Literature summary for 3.4.21.76 extracted from

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 (2016), J. Biol. Chem., 291, 10476-10489 .

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Cloned(Commentary)

Cloned (Comment)	Organism
stable recombinant expression fo wild-type and mutant enzymes in rat basophilic leukemia (RBL) cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
H4A	site-directed mutagenesis	Homo sapiens
S204A	site-directed mutagenesis	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
extracellular	-	Homo sapiens	-	-
additional information	during neutrophil activation and apoptosis, membrane expression of PR3 increases, and soluble PR3 is also released into the extracellular environment during degranulation	Homo sapiens	-	-
plasma membrane	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	Homo sapiens	5886	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P24158	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
neutrophil	neutrophil membrane expression of PR3 increases during both activation and apoptosis	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
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	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
PR3	-	Homo sapiens
proteinase 3	-	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	neutrophil membrane expression of PR3 increases during both activation and apoptosis. Membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis	up

General Information

General Information	Comment	Organism
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	Homo sapiens
additional information	enzyme-microvesicle interaction analysis by surface plasmon resonance spectroscopy. Molecular modeling	Homo sapiens
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	Homo sapiens

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Release 2023.1 (January 2023)