Proteinase 3

Proteinase 3
	according to PDB 1FUJ
	Existing structural data: 1fuj
Properties of human protein
Mass / length primary structure	221 aa; 24.2 kDa
Identifier
Gene names	PRTN3 ; PR3; ACPA; AGP7; C-ANCA; MBT; P29; PR-3
External IDs	OMIM : 177020 ; UniProt : P24158 ; MGI : 893580 ;
Enzyme classification
EC, category	3.4.21.76 , serine protease
MEROPS	S01.134
Response type	Hydrolysis of proteins including elastin
Substrate	Protein with amino acid -Ala - + - Xaa- or -Val - + - Xaa-
Products	Fission products
Occurrence
Homology family	Trypsin precursor
Parent taxon	Creature
	Orthologue

Proteinase 3 (PR3, myeloblastin) is an enzyme in fish and four-legged friends ( Euteleostomi , which taxonomically includes humans), which plays a role in the immune system with its antimicrobial effect . It is a serine protease that is related to neutrophil elastase (ELA2) and azurocidin (AZU), is encoded on the same gene segment and is built into neutrophils together with them . In an autoimmune disease in humans, granulomatosis with polyangiitis , antibodies are formed against the enzyme.

synthesis

The PR3 gene on chromosome 19 is distributed over 6.5 kilobases and 5 exons . The transcript has a length of 1001 bases and codes for 256 amino acids which, after splicing the signal sequence and the propeptide, result in a protein with 221 amino acids and 24 kDa molar mass. N- glycosylation at amino acids 129 and 174 (calculated from the unspliced protein) finally produces the 29 kDa proteinase 3, a cationic glycoprotein .

Biological function

Proteinase 3 is a component of the primary (azurophilic, α-) granules of the neutrophilic granulocytes and lysosomes of the monocytes . The enzyme can be detected in the early stages of development of monocytes and granulocytes. If granulocytes are activated, the α-granules fuse with the cell membrane and thus release proteinase 3. In vitro this effect can be triggered by TNF-α. Proteinase 3 has proteolytic properties and cleaves z. B. elastin , fibronectin , laminin , hemoglobin and collagen type IV . Proteinase 3 has an antimicrobial effect against E. coli and C. albicans and is involved in the maturation of myeloid cells . The natural inhibitor of proteinase 3 is α-1 antitrypsin .

literature

Lothar Thomas: Labor und Diagnose 5th Edition, Frankfurt / Main 2000, ISBN 3-98052155-9

Individual evidence

^ Proteinase 3. In: Online Mendelian Inheritance in Man . (English).
↑ Ensembl entry
↑ UniProt P24158 .
↑ von Vietinghoff S, Eulenberg C, Wellner M, Luft FC, Kettritz R: Neutrophil surface presentation of the anti-neutrophil cytoplasmic antibody-antigen proteinase 3 depends on N-terminal processing . In: Clin. Exp. Immunol. . 152, No. 3, June 2008, pp. 508-16. doi : 10.1111 / j.1365-2249.2008.03663.x . PMID 18462208 .
↑ Peikert T, Finkielman JD, Hummel AM, et al : Functional characterization of antineutrophil cytoplasmic antibodies in patients with cocaine-induced midline destructive lesions . In: Arthritis Rheum . 58, No. 5, May 2008, pp. 1546-51. doi : 10.1002 / art.23469 . PMID 18438818 .
↑ Kallenberg CG: Pathogenesis of PR3-ANCA associated vasculitis . In: J. Autoimmune. . 30, No. 1-2, 2008, pp. 29-36. doi : 10.1016 / j.jaut.2007.11.005 . PMID 18162369 .
↑ Hajjar E, Mihajlovic M, Witko-Sarsat V, Lazaridis T, Reuter N: Computational prediction of the binding site of proteinase 3 to the plasma membrane . In: Proteins . 71, No. 4, June 2008, pp. 1655-69. doi : 10.1002 / prot.21853 . PMID 18076025 .
↑ Korkmaz B, Moreau T, Gauthier F: Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions . In: Biochemistry . 90, No. 2, February 2008, pp. 227-42. doi : 10.1016 / j.biochi.2007.10.009 . PMID 18021746 .
↑ Müller A, Voswinkel J, Gottschlich S, Csernok E: Human proteinase 3 (PR3) and its binding molecules: implications for inflammatory and PR3-related autoimmune responses . In: Ann. NY Acad. Sci. . 1109, August 2007, pp. 84-92. doi : 10.1196 / annals.1398.010 . PMID 17785293 .
^ Sugawara S: Immune functions of proteinase 3 . In: Crit. Rev. Immunol. . 25, No. 5, 2005, pp. 343-60. PMID 16167885 .
↑ Wu YY, Hsu TC, Chen TY, et al : Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection . In: Clin. Exp. Immunol. . 128, No. 2, May 2002, pp. 347-52. PMID 11985526 . PMC 1906401 (free full text).
↑ He Y, Young PK, Grinnell F: Identification of proteinase 3 as the major caseinolytic activity in acute human wound fluid . In: Journal of Investigative Dermatology . 110, No. 1, January 1998, pp. 67-71. doi : 10.1046 / j.1523-1747.1998.00075.x . PMID 9424090 .

[1] Proteinase 3. In: Online Mendelian Inheritance in Man . (English).

[2] Ensembl entry

[3] UniProt P24158 .

[4] von Vietinghoff S, Eulenberg C, Wellner M, Luft FC, Kettritz R: Neutrophil surface presentation of the anti-neutrophil cytoplasmic antibody-antigen proteinase 3 depends on N-terminal processing . In: Clin. Exp. Immunol. . 152, No. 3, June 2008, pp. 508-16. doi : 10.1111 / j.1365-2249.2008.03663.x . PMID 18462208 .

[5] Peikert T, Finkielman JD, Hummel AM, et al : Functional characterization of antineutrophil cytoplasmic antibodies in patients with cocaine-induced midline destructive lesions . In: Arthritis Rheum . 58, No. 5, May 2008, pp. 1546-51. doi : 10.1002 / art.23469 . PMID 18438818 .

[6] Kallenberg CG: Pathogenesis of PR3-ANCA associated vasculitis . In: J. Autoimmune. . 30, No. 1-2, 2008, pp. 29-36. doi : 10.1016 / j.jaut.2007.11.005 . PMID 18162369 .

[7] Hajjar E, Mihajlovic M, Witko-Sarsat V, Lazaridis T, Reuter N: Computational prediction of the binding site of proteinase 3 to the plasma membrane . In: Proteins . 71, No. 4, June 2008, pp. 1655-69. doi : 10.1002 / prot.21853 . PMID 18076025 .

[8] Korkmaz B, Moreau T, Gauthier F: Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions . In: Biochemistry . 90, No. 2, February 2008, pp. 227-42. doi : 10.1016 / j.biochi.2007.10.009 . PMID 18021746 .

[9] Müller A, Voswinkel J, Gottschlich S, Csernok E: Human proteinase 3 (PR3) and its binding molecules: implications for inflammatory and PR3-related autoimmune responses . In: Ann. NY Acad. Sci. . 1109, August 2007, pp. 84-92. doi : 10.1196 / annals.1398.010 . PMID 17785293 .

[10] Sugawara S: Immune functions of proteinase 3 . In: Crit. Rev. Immunol. . 25, No. 5, 2005, pp. 343-60. PMID 16167885 .

[11] Wu YY, Hsu TC, Chen TY, et al : Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection . In: Clin. Exp. Immunol. . 128, No. 2, May 2002, pp. 347-52. PMID 11985526 . PMC 1906401 (free full text).

[12] He Y, Young PK, Grinnell F: Identification of proteinase 3 as the major caseinolytic activity in acute human wound fluid . In: Journal of Investigative Dermatology . 110, No. 1, January 1998, pp. 67-71. doi : 10.1046 / j.1523-1747.1998.00075.x . PMID 9424090 .