Proteinase 3

PRTN3
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1FUJ
Identifiers
Aliases	PRTN3, ACPA, AGP7, C-ANCA, CANCA, MBN, MBT, NP-4, NP4, P29, PR-3, PR3, proteinase 3
External IDs	OMIM: 177020; MGI: 893580; HomoloGene: 120934; GeneCards: PRTN3; OMA:PRTN3 - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	848,175 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	79,719,008 bp
RNA expression pattern
	Top expressed in
	bone marrow; ; bone marrow cells; ; spleen; ; blood; ; monocyte; ; granulocyte; ; right lung; ; superior frontal gyrus; ; right frontal lobe; ; dorsolateral prefrontal cortex;
	Top expressed in
	tibiofemoral joint; ; granulocyte; ; fetal liver hematopoietic progenitor cell; ; body of femur; ; bone marrow; ; ankle joint; ; blastocyst; ; embryo; ; human fetus; ; embryo;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	enzyme binding; peptidase activity; serine-type peptidase activity; hydrolase activity; protein binding; serine-type endopeptidase activity; signaling receptor binding;
Cellular component	extracellular matrix; plasma membrane; extracellular exosome; cytosol; extracellular region; extracellular space; azurophil granule lumen; plasma membrane raft; membrane; membrane raft; collagen-containing extracellular matrix;
Biological process	collagen catabolic process; blood coagulation; negative regulation of phagocytosis; mature conventional dendritic cell differentiation; positive regulation of cell population proliferation; antimicrobial humoral response; neutrophil degranulation; proteolysis; membrane protein ectodomain proteolysis; positive regulation of GTPase activity; cell-cell junction maintenance; neutrophil extravasation; phagocytosis; cytokine-mediated signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	5657
	19152
	ENSG00000277804; ENSG00000196415
	ENSMUSG00000057729
	P24158
	Q61096
	NM_002777
	NM_011178
	NP_002768
	NP_035308
	Wikidata
View/Edit Human	View/Edit Mouse

Proteinase 3, also known as PRTN3, is an enzyme that in humans is encoded by the PRTN3 gene.^[5]

Function

PRTN3 is a serine protease enzyme expressed mainly in neutrophil granulocytes. Its exact role in the function of the neutrophil is unknown, but, in human neutrophils, proteinase 3 contributes to the proteolytic generation of antimicrobial peptides. It is also the target of anti-neutrophil cytoplasmic antibodies (ANCAs) of the c-ANCA (cytoplasmic subtype) class, a type of antibody frequently found in the disease granulomatosis with polyangiitis.^[6]

References

^ ^a ^b ^c ENSG00000196415 GRCh38: Ensembl release 89: ENSG00000277804, ENSG00000196415 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000057729 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE (December 1990). "Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils". The Journal of Experimental Medicine. 172 (6): 1709–15. doi:10.1084/jem.172.6.1709. PMC 2188764. PMID 2258701.
^ Hilhorst M, van Paassen P, Tervaert JW (October 2015). "Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis". Journal of the American Society of Nephrology. 26 (10): 2314–27. doi:10.1681/ASN.2014090903. PMC 4587702. PMID 25956510.

Martin KR, Witko-Sarsat V (September 2017). "Proteinase 3: the odd one out that became an autoantigen". Journal of Leukocyte Biology. 102 (3): 689–698. doi:10.1189/jlb.3MR0217-069R. PMID 28546501.
van der Helm-van Mil AH, Huizinga TW, de Vries RR, Toes RE (June 2007). "Emerging patterns of risk factor make-up enable subclassification of rheumatoid arthritis". Arthritis and Rheumatism. 56 (6): 1728–35. doi:10.1002/art.22716. PMID 17534941.
Kettritz R (September 2016). "Neutral serine proteases of neutrophils". Immunological Reviews. 273 (1): 232–48. doi:10.1111/imr.12441. PMID 27558338. S2CID 29724551.</ref>
Zimmer M, Medcalf RL, Fink TM, Mattmann C, Lichter P, Jenne DE (September 1992). "Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter". Proceedings of the National Academy of Sciences of the United States of America. 89 (17): 8215–9. Bibcode:1992PNAS...89.8215Z. doi:10.1073/pnas.89.17.8215. PMC 49888. PMID 1518849.
Cornec D, Cornec-Le Gall E, Fervenza FC, Specks U (October 2016). "ANCA-associated vasculitis - clinical utility of using ANCA specificity to classify patients". Nature Reviews. Rheumatology. 12 (10): 570–9. doi:10.1038/nrrheum.2016.123. PMID 27464484. S2CID 22205737.
Rao NV, Wehner NG, Marshall BC, Gray WR, Gray BH, Hoidal JR (May 1991). "Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties". The Journal of Biological Chemistry. 266 (15): 9540–8. doi:10.1016/S0021-9258(18)92854-1. PMID 2033050.
Ohlsson K, Linder C, Rosengren M (July 1990). "Monoclonal antibodies specific for neutrophil proteinase 4. Production and use for isolation of the enzyme". Biological Chemistry Hoppe-Seyler. 371 (7): 549–55. doi:10.1515/bchm3.1990.371.2.549. PMID 2121162.
Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE (December 1990). "Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils". The Journal of Experimental Medicine. 172 (6): 1709–15. doi:10.1084/jem.172.6.1709. PMC 2188764. PMID 2258701.
Goldschmeding R, Dolman KM, van den Ende ME, van der Meer-Gerritsen CH, Sonnenberg A, von dem Borne AE (1991). "The relation of 29 kD C-ANCA antigen to proteinase 3". APMIS. 98 (S19): 26–7. doi:10.1111/j.1600-0463.1990.tb05713.x. PMID 2285532. S2CID 37665338.
Wilde CG, Snable JL, Griffith JE, Scott RW (February 1990). "Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase". The Journal of Biological Chemistry. 265 (4): 2038–41. doi:10.1016/S0021-9258(19)39936-3. PMID 2404977.
Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF (July 1989). "Antibiotic proteins of human polymorphonuclear leukocytes". Proceedings of the National Academy of Sciences of the United States of America. 86 (14): 5610–4. Bibcode:1989PNAS...86.5610G. doi:10.1073/pnas.86.14.5610. PMC 297672. PMID 2501794.
Bories D, Raynal MC, Solomon DH, Darzynkiewicz Z, Cayre YE (December 1989). "Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells". Cell. 59 (6): 959–68. doi:10.1016/0092-8674(89)90752-6. PMID 2598267.
Pontremoli S, Melloni E, Michetti M, Sacco O, Sparatore B, Salamino F, Damiani G, Horecker BL (March 1986). "Cytolytic effects of neutrophils: role for a membrane-bound neutral proteinase". Proceedings of the National Academy of Sciences of the United States of America. 83 (6): 1685–9. Bibcode:1986PNAS...83.1685P. doi:10.1073/pnas.83.6.1685. PMC 323148. PMID 3513185.
Sugimori T, Cooley J, Hoidal JR, Remold-O'Donnell E (September 1995). "Inhibitory properties of recombinant human monocyte/neutrophil elastase inhibitor". American Journal of Respiratory Cell and Molecular Biology. 13 (3): 314–22. doi:10.1165/ajrcmb.13.3.7654387. PMID 7654387.
Brunini F, Page TH, Gallieni M, Pusey CD (November 2016). "The role of monocytes in ANCA-associated vasculitides" (PDF). Autoimmunity Reviews. 15 (11): 1046–1053. doi:10.1016/j.autrev.2016.07.031. hdl:10044/1/39150. PMID 27491570.

External links

Proteinase+3 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] ENSG00000196415 GRCh38: Ensembl release 89: ENSG00000277804, ENSG00000196415 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000057729 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid2258701-5] Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE (December 1990). "Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils". The Journal of Experimental Medicine. 172 (6): 1709–15. doi:10.1084/jem.172.6.1709. PMC 2188764. PMID 2258701.

[Hilhorst2015-6] Hilhorst M, van Paassen P, Tervaert JW (October 2015). "Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis". Journal of the American Society of Nephrology. 26 (10): 2314–27. doi:10.1681/ASN.2014090903. PMC 4587702. PMID 25956510.

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v t e Endopeptidases: serine proteases/serine endopeptidases (EC 3.4.21)
Digestive enzymes	Enteropeptidase Trypsin Chymotrypsin Elastase Neutrophil Pancreatic
Coagulation	factors: Thrombin Factor VIIa Factor IXa Factor Xa Factor XIa Factor XIIa Kallikrein PSA KLK1 KLK2 KLK3 KLK4 KLK5 KLK6 KLK7 KLK8 KLK9 KLK10 KLK11 KLK12 KLK13 KLK14 KLK15 fibrinolysis: Plasmin Plasminogen activator Tissue plasminogen activator Urinary plasminogen activator
Complement system	Factor B Factor D Factor I MASP MASP1 MASP2 C3-convertase
Other immune system	Chymase Granzyme Tryptase Proteinase 3/Myeloblastin
Venombin	Ancrod Batroxobin
Other	Acrosin Prolyl endopeptidase Pronase Proprotein convertases 1 2 Prostasin Reelin Subtilisin/Furin/S1P4 Sedolisin/TPP1 Streptokinase Cathepsin A G

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Function

References

Further reading

External links