Literature summary for 3.4.21.76 extracted from

Hu, N.; Westra, J.; Kallenberg, C.G.
Membrane-bound proteinase 3 and its receptors: relevance for the pathogenesis of Wegeners Granulomatosis (2009), Autoimmun. Rev., 8, 510-514.

Search for more literature for 3.4.21.76

Application

Application	Comment	Organism
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	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
alpha1-antitrypsin	endogenous inhibitor of PR3	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
membrane	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	Homo sapiens	16020	-
additional information	large amounts in granules	Homo sapiens	-	-
vesicle	large amounts	Homo sapiens	31982	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
neutrophil	-	Homo sapiens	-

Substrates and Products (Substrate)

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

Synonyms

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

Expression

Organism	Comment	Expression
Homo sapiens	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	up

General Information

General Information	Comment	Organism
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	Homo sapiens

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Release 2023.1 (January 2023)