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Information on EC 3.4.21.76 - Myeloblastin
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3.4.21.76 MyeloblastinSpecify your search results
Word Map
- 3.4.21.76
-
ancas
- myeloperoxidase
-
antineutrophil
- elastase
- autoantibody
- cathepsin
-
anca-associated
-
pr3-anca
- proteases
- granule
- renal
- polyangiitis
- autoimmune
- glomerulonephritis
-
mpo-anca
- vasculitides
-
remission
- autoantigens
- anti-pr3
-
azurophilic
-
crescent
-
perinuclear
- cyclophosphamide
-
vasculitic
-
granulomatous
- lactoferrin
- gpa
-
anti-mpo
-
churg-strauss
-
anca-positive
-
pauci-immune
-
antinuclear
-
neutrophil-derived
- elafin
- polyarteritis
-
small-vessel
-
antibody-associated
-
anti-proteinase
-
azurocidin
-
anti-myeloperoxidase
-
ethanol-fixed
-
chapel
- medicine
- analysis
-
necrotising
-
leukemia-specific
- nodosa
- anti-gbm
- diagnostics
- drug development
-
aspartate-specific
-
anti-glomerular
-
goodpasture
-
mpo-anca-associated
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-/- > -Val-/-
Synonyms
AGP7, C-ANCA antigen, human leukocyte proteinase 3, human proteinase 3, Leukocyte proteinase 3, Leukocyte proteinase 4, myeloblastin, neutrophil protease PR3, neutrophil proteinase 3, P29, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AGP7
-
-
-
-
C-ANCA antigen
-
-
-
-
Leukocyte proteinase 3
-
-
-
-
Leukocyte proteinase 4
-
-
-
-
myeloblastin
neutrophil proteinase 3
P29
-
-
-
-
p29b
PMNL proteinase
-
-
-
-
PR3
proteinase 3
Proteinase PR-3
-
-
-
-
Proteinase-3
Wegener's autoantigen
-
-
-
-
Wegener's granulomatosis autoantigen
-
-
-
-
PR3
-
-
-
-
PR3
-
-
PR3
-
proteinase 3
-
-
proteinase 3
-
Proteinase-3
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-/- > -Val-/-
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
128028-50-2
-
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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
(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
?
-
-
-
?
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-(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-Tyr-Tyr-Abu-ANB-NH2 + H2O
?
-
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
-
-
?
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-Val-Ala-Asp-Nvl-Ala-Asp-Arg-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
-
?
Ahx-PYFA-4-nitroanilide + H2O
?
-
the reaction is inhibited by antibody MCPR3-7 binding
-
-
?
annexin 1 + H2O
?
-
proteinase 3 is the main enzyme responsible for cleavage in the N terminus region of the protein
-
-
?
Boc-Ala-ONp + H2O
?
-
the reaction is not inhibited by antibody MCPR3-7 binding
-
-
?
Boc-Ala-Pro-nVal-SBzl + H2O
?
-
the reaction is not inhibited by antibody MCPR3-7 binding
-
-
?
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 18.5–102 nanomol)
-
-
?
For-Ala-Ala-Pro-Abu-SBzl + H2O
?
-
the reaction is partly inhibited by antibody MCPR3-7 binding
-
-
?
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
-
-
?
MeO-Suc-Ala-Ala-Pro-Val-4-nitroanilide + H2O
MeO-Suc-Ala-Ala-Pro-Val + 4-nitroaniline
-
-
-
-
?
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
-
-
?
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
-
-
-
Abz-VADCADQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 614/mM/s
-
-
?
Boc-Ala-Pro-Nva-thiobenzylester + H2O
?
-
pH 7.5, serine-protease activity of PR3
-
-
?
Boc-Ala-Pro-Nva-thiobenzylester + H2O
?
pH 7.5, serine-protease activity of PR3
-
-
?
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-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
-
-
?
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
-
-
?
oxidized insulin B chain + H2O
?
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
-
-
?
oxidized insulin B chain + H2O
?
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
-
-
?
procaspase-3 + H2O
?
-
37°C
in vitro, purified PR3 cleaves procaspase-3 into an active 22 kDa fragment
-
?
procaspase-3 + H2O
?
-
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-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
-
-
?
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-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
-
-
?
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
-
-
?
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
-
-
?
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
?
-
-
substrate specificity for small hydrophobic residues at P1 position (Val, Cys, Ala, Met, Ser and Leu)
-
-
-
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
-
-
-
additional information
?
-
-
in mouse PR3 binding sites S6, S5, S1' and S3' are clearly polar, S2' is pretty polar, while S4, S3, S1, S4' are rather hydrophobic. VADVKDR does not interact properly with mouse PR3
-
-
-
additional information
?
-
-
unlike human PR3, mouse PR3 is unlikely to bind substrates with acidic groups (Asp, Glu) on the S side. Efficient substrates of human PR3 may be poor substrates of mouse PR3
-
-
-
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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
?
-
-
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
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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
(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
-
-
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-proteinase
-
does not inhibit when PR3 is bound to the outer cell surface of neutrophils
-
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
-
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
-
-
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%
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
-
[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%
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-antitrypsin
-
inhibition of bilayer-bound PR3 is more important than that observed for the soluble form of the enzyme
-
alpha1-antitrypsin
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 0.74 M
-
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
-
alpha1-protease inhibitor
-
purified human alpha1-protease inhibitor inhibits gibbon PR3 and forms a covalently linked complex with it
-
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
-
Eglin c
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 117 M
Eglin c
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 3.3 M
elafin
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 1.9 M
-
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
-
elafin
-
is inhibited by purified human elafin, a canonical low molecular weight inhibitor of human PR3
-
elafin
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 0.99 M
-
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
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
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
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
-
Val15-aprotinin
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 447 M
-
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
-
not: alpha1-anti-chymotrypsin; secretory leukocyte proteinase inhibitor
-
additional information
-
aprotinin; cysteine, aspartic, or metalloproteinase inhibitors; secretory leukocyte proteinase inhibitor
-
additional information
-
membrane-bound enzyme is resistant to inhibition by physiologic proteinase inhibitors
-
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
-
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
-
additional information
-
synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogues as dual inhibitors of neutrophil elastase and proteinase 3, structure–activity relationship analysis, overview
-
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
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
-
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
-
PRTN3235-specific T-cells can be stimulated from the blood of healthy individuals with multiple HLA-DR-genotypes
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.61
Suc-AAA-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
3.5
Suc-AAPL-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
additional information
additional information
-
Km values of peptidyl thiobenzyl esters
-
1.1
MeOSuc-AAPV-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
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
1.5
MeOSuc-AIPM-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
2.5
Suc-AAPV-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
3.7
Suc-AAPV-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
0.031
Suc-AAA-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.16
Suc-AAPL-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
additional information
additional information
-
turnover numbers of peptidyl thiobenzyl esters
-
0.59
MeOSuc-AAPV-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
6.2
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
7.2
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
11.2
Suc-AAPV-4-nitroanilide
-
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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)
-
-
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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
-
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4’-dithiodipyridine
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00173
(E)-4-(N-(2-(1-(hydroxyimino)butyl)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 7.4, 30°C
0.00053
(E)-4-(N-(2-(1-(hydroxyimino)methyl)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 7.4, 30°C
0.00061
(E)-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 7.4, 30°C
0.00061
2-hydroxyethyl 2-(4-(pivaloyloxy)phenylsulfonamido)benzoate
Homo sapiens
-
pH 7.4, 30°C
0.00031
4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
-
pH 7.4, 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-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
-
pH 7.4, 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
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)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 7.4, 30°C
0.01
propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
-
pH 7.4, 30°C
447000
Val15-aprotinin
Mus musculus
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 447 M
-
740
alpha1-antitrypsin
Mus musculus
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 0.74 M
-
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
-
3300
Eglin c
Mus musculus
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 3.3 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
990
elafin
Mus musculus
-
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 0.99 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
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
29718, 29719, 29720, 29721, 29722, 29724, 29726, 684453, 685785, 686188, 686192, 686753, 687439, 687566, 687618, 687927, 688215, 688708, 697411, 698376, 707117, 707129, 707316, 707322, 707338, 707736, 708497, 709030, 709349, 709372, 709431, 709688, 709758, 710661, 717507, 717575, 717959, 718119
-
-
brenda
-
663599, 663606, 664451, 664822, 664898, 664960, 665530, 665647, 665920, 665985, 666198, 666199, 666751, 683193, 695610, 718191, 731482, 731997, 732115, 732316
SwissProt
brenda
human
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
increased PR-3 on the alveolar macrophage surface in usual interstitial pneumonia relative to healthy controls and sarcoidosis subjects
brenda
-
proteinase 3 is considerably more expressed in bone marrow than in the peripheral blood
brenda
additional information
-
cell associated PR3 levels are lower than in neutrophils, thus sensitivity of the indirect immunofluorescence test is lower
brenda
-
blood neutrophils from patients with active Wegener’s granulomatosis bear greater amounts of PR3 on their cell membranes than do neutrophils from healthy individuals
brenda
-
; targeting to granules is not dependent on glycosylation, but unglycosylated recombinant PR3 gets secreted preferentially into media supernatants
brenda
-
endogenous annexin 1 and PR3 localization in resting and stimulated blood neutrophils
brenda
-
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
brenda
-
neutrophil extracts from vasculitis patients and healthy controls contain comparable amounts of PR3
brenda
-
-
663599, 664822, 664898, 664960, 665530, 665647, 665920, 665985, 666198, 666199, 666751, 686188, 687566, 688708, 707117, 707316, 707322, 707338, 707736, 709758, 731482, 732316
brenda
-
presence of anti-complementary PR3 and anti-PR3 antibodies in human Wegener’s granulomatosis sera
brenda
-
cell associated PR3 levels are lower than in neutrophils, thus sensitivity of the indirect immunofluorescence test is lower
brenda
additional information
-
neutrophil-dereived PR3 is more potent than urinary PR3
brenda
additional information
-
mRNA for PR3 is transcribed in the promyelocyte and promonocyte stages of myeloid differentiation. Present in mastocytes and no-hematopoietic cell
brenda
additional information
-
PR3 antigen is usually present in granulomas and antigen-presenting cells are found in these lesions as well
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
from human polymorphonuclear leukocytes (PMNL)
brenda
-
major pool of intracellular PR3 is within the azurophilic granules
brenda
-
a major neutrophilic serine protease expressed in neutrophil azurophil granules
brenda
-
strong correlation between PR3 and CD177 surface expression
brenda
-
-
brenda
-
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
brenda
-
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
brenda
-
behaves as a peripheral membrane protein. The mouse form is globally more electronegative than the human form. As a consequence of differences in sequence and structural properties, mouse PR3 is likely to be able to bind to the plasma membrane using the same region as human PR3, although less strongly and specifically
brenda
-
PR3 and CD177 exhibit a dynamic plasma membrane expression with rapid internalization and re-expression
brenda
-
the extragranular pool of PR3, which is externalized during apoptosis, may be functionally very important in the pathophysiology of vasculitis
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
neutrophil serine proteases, proteinase 3 and human neutrophil elastase, share high sequence similarity, but have different substrate specificities and functions
malfunction
metabolism
physiological function
additional information
-
proteinase 3 is an abundant serine protease with high similarity to neutrophil elastase
malfunction
-
in mice lacking neutrophil serine PR3 (DPPI-/- mice), inhibition of caspase 1 activity results in decreased bioactive IL-1beta concentrations in the synovial tissue and less suppression of chondrocyte anabolic function. Dual blockade of both PR3 and caspase 1 leads to protection against cartilage and bone destruction. Deficiency of PR3 in combination with inhibition of caspase 1 does not reduce the joint swelling in streptococcal cell wall-induced acute arthritis
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
-
all c-ANCA-positive samples (diagnosed Wegener granulomatosis) show a significant increase of PR3 activity
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
-
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
-
caspase 1-independent processing of IL-1beta occurs in arthritis by serine proteases such as PR3
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
-
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
-
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
-
neutrophil-derived PR3 can induce kallikrein-independent activation of the kinin pathway
physiological function
-
anti-neutrophil cytoplasmic antibodies (cANCAs) from Wegener’s 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
-
gibbon PR3 shows an intermediate anti-neutrophil cytoplasmic antibody (cANCA) binding pattern, whereas some anti-PR3 mouse antibodies and some patient sera recognize the antigen. The cANCAs from Wegener’s 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
-
macaque PR3 shows nearly no reactivity to anti-neutrophil cytoplasmic antibodies (cANCAs)
physiological function
-
almost complete absence of anti-neutrophil cytoplasmic antibody (cANCA) binding to rhesus monkey PR3
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
-
occurrence of anti-neutrophil-cytoplasmic antibodies (ANCA) directed against proteinase-3 is a hallmark of Wegener’s 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
-
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
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
-
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
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
30000
additional information
-
processing of proteinase 3 in U937 human myelomonocytic cell line: a 35000 MW precursor is converted into a 29000 MW mature form
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
pro-PR3 is found to constitute 10% of circulating PR3 but none of the membrane-PR3
proteolytic modification
-
the pro-enzyme zymogen has to be proteolytically activated
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
Sap3 in a stable complex with pepstatin A and in the absence of an inhibitor, in the presence of Zn2+, to 1.9 and 2.2 A resolution. Inhibitor binding causes active site closure by the movement of a flap segment. Sap3 consists of the S2' binding site becoming channelshaped subsequent to the turn of the loop with residues 129–135
-
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
-
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
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
S195A
-
site-directed mutagenesis, cDNA construction of a catalytically inactive active site enyzme mutant lacking the codons for the N-terminal activation dipeptide, DELTAPR3ctp-S195A
S203A
V35M/S38AN/I38BP/Q74R/N113K/N159K/119-122QVAS
-
results in the gibbon proteinase 3 variant 2. Is no longer able to interact with the mouse antibodies 4A5 and WGM2, but retains its binding to CLB12.8
V35M/S38AN/L39BP/Q74R
-
results in the gibbon proteinase 3 variant 1. The binding site for mouse antibody CLB12.8, but not that for MCPR3-2, is reconstituted. Binds also to mouse antibody 6A6. Like MCPR3-2, WGM3 binds neither to gibbon PR3 nor to the humanized gibbon proteinase 3 variant 1
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
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
6 x His-tagged proPR3 purified using affinity chromatography
-
-
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CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
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
-
expression in HMC-1 cells and 293 cells
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
-
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
-
granulocyte cDNA amplified, PCR fragment reamplified and cloned into pcDNA5/FRT. Human/gibbon chimeras performed by digestion of pcDNA5/FRT/PR3-H6 with BlpI and AgeI and exchange of the respective cDNA segments. Chemically synthesized 390-bp human PR3 fragment digested with PmlI/BlpI and cloned into the same sites of the pcDNA5/FRT/gPR3-H6 plasmid to reconstruct the human CLB12.8 epitope in gibbon PR3 (gibbon proteinase 3 variant 1). A further modification of this variant by replacing the A116 to Q119 tetrapeptide with the respective opossum residues Q-V-A-S. To this end, a DNA fragment chemically synthesized, digested with BlpI and BstEII, and subcloned into the same sites of the gPR3v1 plasmid. The two glycosylation sites Asn113 and Asn159 mutated to lysine residues in the gibbon proteinase 3 variant 2. 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
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
additional information
-
design of potent and highly specific substrates of proteinase 3 and other proteinases optimized in the prime site region
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
-
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
-
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
-
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
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
medicine
-
major target autoantigen in patients with Wegener's granulomatosis, a systemic vasculitis
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 Wegener’s granulomatosis
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
-
proinflammatory role of membrane PR3 expression may involve interference with macrophage clearance of apoptotic neutrophils
medicine
-
PR3 induces DC maturation via protease-activated receptor-2. Wegener’s 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 Wegener’s granulomatosis. PR3-anti-neutrophil cytoplasmic antibodies are strongly associated with Wegener’s 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 Wegener’s granulomatosis is not yet available
medicine
-
PR3-anti-neutrophil cytoplasmic antibodies from Wegener’s granulomatosis patients do not recognize the natively folded murine PR3
medicine
-
in patients with Wegener’s granulomatosis, epitope recognition by anti-neutrophil cytoplasmic antibodies (ANCA) is affected by the glycosylation status of PR3
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 Wegener’s granulomatosis and polycythemia vera
medicine
-
down-regulation of anticoagulation during inflammation by rapid endothelial cell protein C receptor proteolysis by PR3
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
medicine
-
extra-intestinal pulmonary complications of ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody resembling Wegener’s granulomatosis and spontaneous improvement
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
-
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
-
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
-
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
-
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
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
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JOURNAL
VOL.
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YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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336
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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
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6
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1998
Homo sapiens
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He, S.; Kuang, R.; Venkataraman, R.; Tu, J.; Truong, T.M.; Chan, H.K.; Groutas, W.C.
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8
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2000
Homo sapiens
brenda
Goldmann, W.H.; Niles, J.L.; Arnaout, M.A.
Interaction of purified human proteinase 3 (PR3) with reconstituted lipid bilayers
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261
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1999
Homo sapiens
brenda
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
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277
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Homo sapiens, Rattus norvegicus
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Compared action of neutrophil proteinase 3 and elastase on model substrates. Favorable effect of S'-P' interactions on proteinase 3 catalysts
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278
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Stummann, L.; Wiik, A.
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206
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30
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brenda
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, Homo sapiens (P24158)
brenda
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
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107
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Homo sapiens, Homo sapiens (P24158)
brenda
Zani, M.L.; Nobar, S.M.; Lacour, S.A.; Lemoine, S.; Boudier, C.; Bieth, J.G.; Moreau, T.
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271
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Homo sapiens, Homo sapiens (P24158)
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Homo sapiens, Homo sapiens (P24158), Mus musculus, Mus musculus (Q61096)
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49
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Proteinase 3 is an IL-32 binding protein
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103
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Homo sapiens, Homo sapiens (P24158)
brenda
Korkmaz, B.; Moreau, T.; Gauthier, F.
Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions
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34
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Hajjar, E.; Korkmaz, B.; Reuter, N.
Differences in the substrate binding sites of murine and human proteinase 3 and neutrophil elastase
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581
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2007
Homo sapiens, Mus musculus, Rattus norvegicus
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Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies
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Korkmaz, B.; Hajjar, E.; Kalupov, T.; Reuter, N.; Brillard-Bourdet, M.; Moreau, T.; Juliano, L.; Gauthier, F.
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282
1989-1997
2007
Homo sapiens
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Borelli, C.; Ruge, E.; Schaller, M.; Monod, M.; Korting, H.C.; Huber, R.; Maskos, K.
The crystal structure of the secreted aspartic proteinase 3 from Candida albicans and its complex with pepstatin A
Proteins
68
738-748
2007
Candida albicans
brenda
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, Homo sapiens (P24158)
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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, Hylobates pileatus, Macaca mulatta, Pan troglodytes verus
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Broemstrup, T.; Reuter, N.
How does proteinase 3 interact with lipid bilayers?
Phys. Chem. Chem. Phys.
12
7487-7496
2010
Homo sapiens (P24158)
brenda
Relle, M.; Thomaidis, T.; Galle, P.R.; Schwarting, A.
Comparative aspects of murine proteinase 3
Rheumatol. Int.
31
1105-1111
2011
Mus musculus, Mus musculus (Q61096)
brenda
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, Homo sapiens (P24158)
brenda
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, Homo sapiens (P24158)
brenda
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)
brenda
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, Homo sapiens (P24158)
brenda
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