PRTN3_HUMAN
ID PRTN3_HUMAN Reviewed; 256 AA.
AC P24158; P15637; P18078; Q4VB08; Q4VB09; Q6LBM7; Q6LBN2; Q9UD25; Q9UQD8;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Myeloblastin;
DE EC=3.4.21.76 {ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245};
DE AltName: Full=AGP7;
DE AltName: Full=C-ANCA antigen;
DE AltName: Full=Leukocyte proteinase 3;
DE Short=PR-3;
DE Short=PR3;
DE AltName: Full=Neutrophil proteinase 4;
DE Short=NP-4;
DE AltName: Full=P29;
DE AltName: Full=Wegener autoantigen;
DE Flags: Precursor;
GN Name=PRTN3; Synonyms=MBN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-119; THR-135 AND SER-136.
RX PubMed=1681549; DOI=10.1073/pnas.88.20.9253;
RA Labbaye C., Musette P., Cayre Y.E.;
RT "Wegener autoantigen and myeloblastin are encoded by a single mRNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:9253-9256(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-119.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-119.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20 AND 22-256.
RX PubMed=1518849; DOI=10.1073/pnas.89.17.8215;
RA Zimmer M., Medcalf R.L., Fink T.M., Mattmann C., Lichter P., Jenne D.E.;
RT "Three human elastase-like genes coordinately expressed in the
RT myelomonocyte lineage are organized as a single genetic locus on 19pter.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:8215-8219(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-254, AND VARIANTS THR-135 AND
RP SER-136.
RX PubMed=1400430; DOI=10.1016/s0021-9258(19)36816-4;
RA Sturrock A.B., Franklin K.F., Rao G., Marshall B.C., Rebentisch M.B.,
RA Lemons R.S., Hoidal J.R.;
RT "Structure, chromosomal assignment, and expression of the gene for
RT proteinase-3. The Wegener's granulomatosis autoantigen.";
RL J. Biol. Chem. 267:21193-21199(1992).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-200, AND VARIANT ILE-119.
RX PubMed=9924693; DOI=10.1097/00002371-199901000-00001;
RA Clave E., Molldrem J., Hensel N., Raptis A., Barrett A.J.;
RT "Donor-recipient polymorphism of the proteinase 3 gene: a potential target
RT for T-cell alloresponses to myeloid leukemia.";
RL J. Immunother. 22:1-6(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-42.
RX PubMed=2001463;
RA Musette P., Labbaye C., Dorner M.H., Cayre Y.E., Casanova J.-L.,
RA Kourilsky P.;
RT "Wegener's autoantigen and leukemia.";
RL Blood 77:1398-1399(1991).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-256, AND PROTEIN SEQUENCE OF 28-71; 156-181
RP AND 196-219.
RX PubMed=2258701; DOI=10.1084/jem.172.6.1709;
RA Campanelli D., Melchior M., Fu Y., Nakata M., Shuman H., Nathan C.,
RA Gabay J.E.;
RT "Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and
RT autoantigen from human neutrophils.";
RL J. Exp. Med. 172:1709-1715(1990).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-256, AND VARIANTS ILE-119; THR-135 AND
RP SER-136.
RX PubMed=2598267; DOI=10.1016/0092-8674(89)90752-6;
RA Bories D., Raynal M.-C., Solomon D.H., Darzynkiewicz Z., Cayre Y.E.;
RT "Down-regulation of a serine protease, myeloblastin, causes growth arrest
RT and differentiation of promyelocytic leukemia cells.";
RL Cell 59:959-968(1989).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-256, PROTEIN SEQUENCE OF 28-48, VARIANTS
RP ILE-119; THR-135 AND SER-136, AND IDENTITY OF WEGENER'S AUTOANTIGEN WITH
RP PR-3.
RX PubMed=2377228; DOI=10.1038/346520a0;
RA Jenne D.E., Tschopp J., Luedemann J., Utecht B., Gross W.L.;
RT "Wegener's autoantigen decoded.";
RL Nature 346:520-520(1990).
RN [12]
RP PROTEIN SEQUENCE OF 28-67 AND 228-244, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=2033050; DOI=10.1016/s0021-9258(18)92854-1;
RA Rao N.V., Wehner N.G., Marshall B.C., Gray W.R., Gray B.H., Hoidal J.R.;
RT "Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase.
RT Structural and functional properties.";
RL J. Biol. Chem. 266:9540-9548(1991).
RN [13]
RP PROTEIN SEQUENCE OF 28-47 AND 196-219.
RX PubMed=2404977; DOI=10.1016/s0021-9258(19)39936-3;
RA Wilde C.G., Snable J.L., Griffith J.E., Scott R.W.;
RT "Characterization of two azurphil granule proteases with active-site
RT homology to neutrophil elastase.";
RL J. Biol. Chem. 265:2038-2041(1990).
RN [14]
RP PROTEIN SEQUENCE OF 28-52.
RX PubMed=2121162; DOI=10.1515/bchm3.1990.371.2.549;
RA Ohlsson K., Linder C., Rosengren M.;
RT "Monoclonal antibodies specific for neutrophil proteinase 4. Production and
RT use for isolation of the enzyme.";
RL Biol. Chem. Hoppe-Seyler 371:549-555(1990).
RN [15]
RP PROTEIN SEQUENCE OF 28-48.
RX PubMed=2285532; DOI=10.1111/j.1600-0463.1990.tb05713.x;
RA Goldschmeding R., Dolman K.M., van den Ende M.E.,
RA van der Meer-Gerritsen C.H., Sonnenberg A., von dem Borne A.E.;
RT "The relation of 29 kD C-ANCA antigen to proteinase 3.";
RL APMIS Suppl. 19:26-27(1990).
RN [16]
RP PROTEIN SEQUENCE OF 28-47.
RX PubMed=2679910;
RA Niles J.L., McCluskey R.T., Ahmad M.F., Arnaout M.A.;
RT "Wegener's granulomatosis autoantigen is a novel neutrophil serine
RT proteinase.";
RL Blood 74:1888-1893(1989).
RN [17]
RP PROTEIN SEQUENCE OF 28-47.
RX PubMed=2501794; DOI=10.1073/pnas.86.14.5610;
RA Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N.,
RA Seeger M., Nathan C.F.;
RT "Antibiotic proteins of human polymorphonuclear leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989).
RN [18]
RP PROTEIN SEQUENCE OF 28-47, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Neutrophil;
RX PubMed=7897245; DOI=10.1016/0022-1759(94)00295-8;
RA Gaskin G., Kendal H., Coulthart A., Turner N., Pusey C.D.;
RT "Use of proteinase 3 purified by reverse phase HPLC to detect
RT autoantibodies in systemic vasculitis.";
RL J. Immunol. Methods 180:25-33(1995).
RN [19]
RP PROTEIN SEQUENCE OF 28-43.
RX PubMed=1688612; DOI=10.1084/jem.171.1.357;
RA Ludemann J., Utecht B., Gross W.L.;
RT "Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize
RT an elastinolytic enzyme.";
RL J. Exp. Med. 171:357-362(1990).
RN [20]
RP PROTEIN SEQUENCE OF 110-121, AND VARIANT ILE-119.
RC TISSUE=Serum;
RX PubMed=7539799; DOI=10.1074/jbc.270.23.14107;
RA Duke-Cohan J.S., Morimoto C., Rocker J.A., Schlossman S.F.;
RT "A novel form of dipeptidylpeptidase IV found in human serum. Isolation,
RT characterization, and comparison with T lymphocyte membrane
RT dipeptidylpeptidase IV (CD26).";
RL J. Biol. Chem. 270:14107-14114(1995).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=3198760; DOI=10.1172/jci113816;
RA Kao R.C., Wehner N.G., Skubitz K.M., Gray B.H., Hoidal J.R.;
RT "Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that
RT produces emphysema in hamsters.";
RL J. Clin. Invest. 82:1963-1973(1988).
RN [22]
RP IDENTITY OF WEGENER'S AUTOANTIGEN WITH PROTEINASE 3.
RX PubMed=2242436;
RA Gupta S.K., Niles J.L., McCluskey R.T., Arnaout M.A.;
RT "Identity of Wegener's autoantigen (p29) with proteinase 3 and
RT myeloblastin.";
RL Blood 76:2162-2162(1990).
RN [23]
RP INTERACTION WITH CD177, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17244676; DOI=10.1182/blood-2006-10-055327;
RA von Vietinghoff S., Tunnemann G., Eulenberg C., Wellner M.,
RA Cristina Cardoso M., Luft F.C., Kettritz R.;
RT "NB1 mediates surface expression of the ANCA antigen proteinase 3 on human
RT neutrophils.";
RL Blood 109:4487-4493(2007).
RN [24]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP INDUCTION.
RX PubMed=18462208; DOI=10.1111/j.1365-2249.2008.03663.x;
RA von Vietinghoff S., Eulenberg C., Wellner M., Luft F.C., Kettritz R.;
RT "Neutrophil surface presentation of the anti-neutrophil cytoplasmic
RT antibody-antigen proteinase 3 depends on N-terminal processing.";
RL Clin. Exp. Immunol. 152:508-516(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21193407; DOI=10.1074/jbc.m110.171256;
RA Jerke U., Rolle S., Dittmar G., Bayat B., Santoso S., Sporbert A., Luft F.,
RA Kettritz R.;
RT "Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA
RT neutrophil activation.";
RL J. Biol. Chem. 286:7070-7081(2011).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22266279; DOI=10.4049/jimmunol.1102540;
RA Kuckleburg C.J., Tilkens S.B., Santoso S., Newman P.J.;
RT "Proteinase 3 contributes to transendothelial migration of NB1-positive
RT neutrophils.";
RL J. Immunol. 188:2419-2426(2012).
RN [28]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23202369; DOI=10.1161/atvbaha.112.300474;
RA Kuckleburg C.J., Newman P.J.;
RT "Neutrophil proteinase 3 acts on protease-activated receptor-2 to enhance
RT vascular endothelial cell barrier function.";
RL Arterioscler. Thromb. Vasc. Biol. 33:275-284(2013).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [30]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CD177, SUBUNIT, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28240246; DOI=10.1038/srep43328;
RA Jerke U., Marino S.F., Daumke O., Kettritz R.;
RT "Characterization of the CD177 interaction with the ANCA antigen proteinase
RT 3.";
RL Sci. Rep. 7:43328-43328(2017).
RN [31]
RP INTERACTION WITH SERPINB1.
RX PubMed=30692621; DOI=10.1038/s41590-018-0303-z;
RA Choi Y.J., Kim S., Choi Y., Nielsen T.B., Yan J., Lu A., Ruan J., Lee H.R.,
RA Wu H., Spellberg B., Jung J.U.;
RT "SERPINB1-mediated checkpoint of inflammatory caspase activation.";
RL Nat. Immunol. 20:276-287(2019).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), GLYCOSYLATION AT ASN-174, AND
RP DISULFIDE BONDS.
RX PubMed=8757293; DOI=10.1006/jmbi.1996.0458;
RA Fujinaga M., Charnaia M.M., Halenbeck R., Koths K., James M.N.G.;
RT "The crystal structure of PR3, a neutrophil serine proteinase antigen of
RT Wegener's granulomatosis antibodies.";
RL J. Mol. Biol. 261:267-278(1996).
CC -!- FUNCTION: Serine protease that degrades elastin, fibronectin, laminin,
CC vitronectin, and collagen types I, III, and IV (in vitro)
CC (PubMed:3198760, PubMed:2033050, PubMed:28240246). By cleaving and
CC activating receptor F2RL1/PAR-2, enhances endothelial cell barrier
CC function and thus vascular integrity during neutrophil transendothelial
CC migration (PubMed:23202369). May play a role in neutrophil
CC transendothelial migration, probably when associated with CD177
CC (PubMed:22266279). {ECO:0000269|PubMed:2033050,
CC ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:23202369,
CC ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:3198760}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins, including elastin, by preferential
CC cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.; EC=3.4.21.76;
CC Evidence={ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:22266279,
CC ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28240246,
CC ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245};
CC -!- ACTIVITY REGULATION: Inhibited by phenylmethanesulfonyl fluoride (PMSF)
CC and diisopropyl fluorophosphate (DFP). {ECO:0000269|PubMed:3198760}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.4. {ECO:0000269|PubMed:3198760};
CC -!- SUBUNIT: May form dimers (PubMed:28240246). Interacts with CD177; the
CC interaction tethers PRTN3 to the cell surface; the interaction is
CC direct (PubMed:17244676, PubMed:28240246). Interacts with SERPINB1
CC (PubMed:30692621). {ECO:0000269|PubMed:17244676,
CC ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:30692621}.
CC -!- INTERACTION:
CC P24158; P24001-4: IL32; NbExp=3; IntAct=EBI-465028, EBI-15570379;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule {ECO:0000269|PubMed:18462208,
CC ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:3198760,
CC ECO:0000269|PubMed:7897245, ECO:0000305|PubMed:17244676}. Secreted
CC {ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:28240246}. Cell
CC membrane {ECO:0000269|PubMed:17244676, ECO:0000269|PubMed:18462208,
CC ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246}; Peripheral
CC membrane protein {ECO:0000269|PubMed:17244676,
CC ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:22266279,
CC ECO:0000269|PubMed:28240246}; Extracellular side
CC {ECO:0000269|PubMed:17244676, ECO:0000269|PubMed:18462208,
CC ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246}. Membrane
CC raft {ECO:0000269|PubMed:21193407}; Peripheral membrane protein
CC {ECO:0000269|PubMed:21193407}; Extracellular side
CC {ECO:0000269|PubMed:21193407}. Note=Localizes predominantly to
CC azurophil granules (primary secretory granules) in neutrophils
CC (PubMed:2033050, PubMed:3198760, PubMed:7897245, PubMed:18462208).
CC Secreted upon neutrophil stimulation by TNF-alpha, lipopolysaccharide
CC (LPS), fMLP and CXCL8/IL8 or during neutrophil transmigration
CC (PubMed:22266279, PubMed:28240246). Following secretion tethered to the
CC cell membrane by CD177 (PubMed:18462208, PubMed:22266279).
CC {ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:2033050,
CC ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246,
CC ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245}.
CC -!- TISSUE SPECIFICITY: Expressed in polymorphonuclear leukocytes (at
CC protein level) (PubMed:2033050, PubMed:7897245, PubMed:3198760).
CC Expressed in neutrophils (at protein level) (PubMed:28240246,
CC PubMed:18462208, PubMed:21193407, PubMed:22266279, PubMed:17244676).
CC Expressed in differentiating neutrophils (PubMed:18462208).
CC {ECO:0000269|PubMed:17244676, ECO:0000269|PubMed:18462208,
CC ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:21193407,
CC ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246,
CC ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245}.
CC -!- INDUCTION: Induced during CSF3/G-CSF-mediated neutrophil
CC differentiation. {ECO:0000269|PubMed:18462208}.
CC -!- DISEASE: Note=Is the major autoantigen in anti-neutrophil cytoplasmic
CC autoantibody (ANCA)-associated vasculitis (Wegener's granulomatosis)
CC (PubMed:2377228, PubMed:2679910). This complex, systemic disease is
CC characterized by granulomatous inflammation with necrotizing lesions in
CC the respiratory tract, glomerulonephritis, vasculitis, and anti-
CC neutrophil cytoplasmatic autoantibodies detected in patient sera
CC (PubMed:2377228, PubMed:2679910). PRTN3 causes emphysema when
CC administered by tracheal insufflation to hamsters (PubMed:3198760).
CC {ECO:0000269|PubMed:3198760, ECO:0000303|PubMed:2377228,
CC ECO:0000303|PubMed:2679910}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Elastase subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36342.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAA39598.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Proteinase 3 entry;
CC URL="https://en.wikipedia.org/wiki/Proteinase_3";
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DR EMBL; M75154; AAA59558.1; -; mRNA.
DR EMBL; AC004799; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69591.1; -; Genomic_DNA.
DR EMBL; BC096183; AAH96183.1; -; mRNA.
DR EMBL; BC096184; AAH96184.1; -; mRNA.
DR EMBL; BC096185; AAH96185.1; -; mRNA.
DR EMBL; BC096186; AAH96186.1; -; mRNA.
DR EMBL; M96628; AAB59364.1; -; Genomic_DNA.
DR EMBL; AH005293; AAB59493.1; -; Genomic_DNA.
DR EMBL; M97911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AH007523; AAD21524.1; -; Genomic_DNA.
DR EMBL; X56606; CAA39943.1; -; mRNA.
DR EMBL; X55668; CAA39203.1; -; mRNA.
DR EMBL; M29142; AAA36342.1; ALT_FRAME; mRNA.
DR EMBL; X56132; CAA39597.1; -; mRNA.
DR EMBL; X56132; CAA39598.1; ALT_INIT; mRNA.
DR CCDS; CCDS32860.1; -.
DR PIR; A45080; PRHU3.
DR RefSeq; NP_002768.3; NM_002777.3.
DR PDB; 1FUJ; X-ray; 2.20 A; A/B/C/D=28-248.
DR PDBsum; 1FUJ; -.
DR AlphaFoldDB; P24158; -.
DR SMR; P24158; -.
DR BioGRID; 111638; 107.
DR DIP; DIP-31107N; -.
DR IntAct; P24158; 7.
DR MINT; P24158; -.
DR STRING; 9606.ENSP00000234347; -.
DR BindingDB; P24158; -.
DR ChEMBL; CHEMBL3900; -.
DR DrugBank; DB05161; Elafin.
DR DrugCentral; P24158; -.
DR GuidetoPHARMACOLOGY; 2401; -.
DR MEROPS; S01.134; -.
DR GlyConnect; 1529; 2 N-Linked glycans (1 site).
DR GlyGen; P24158; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P24158; -.
DR BioMuta; PRTN3; -.
DR DMDM; 6174926; -.
DR CPTAC; non-CPTAC-1142; -.
DR EPD; P24158; -.
DR jPOST; P24158; -.
DR MassIVE; P24158; -.
DR PaxDb; P24158; -.
DR PeptideAtlas; P24158; -.
DR PRIDE; P24158; -.
DR ProteomicsDB; 54192; -.
DR ABCD; P24158; 4 sequenced antibodies.
DR Antibodypedia; 1069; 540 antibodies from 39 providers.
DR DNASU; 5657; -.
DR Ensembl; ENST00000234347.10; ENSP00000234347.3; ENSG00000196415.10.
DR Ensembl; ENST00000612112.4; ENSP00000478977.1; ENSG00000277804.4.
DR GeneID; 5657; -.
DR KEGG; hsa:5657; -.
DR MANE-Select; ENST00000234347.10; ENSP00000234347.3; NM_002777.4; NP_002768.3.
DR UCSC; uc002lqa.2; human.
DR CTD; 5657; -.
DR DisGeNET; 5657; -.
DR GeneCards; PRTN3; -.
DR HGNC; HGNC:9495; PRTN3.
DR HPA; ENSG00000196415; Tissue enriched (bone).
DR MalaCards; PRTN3; -.
DR MIM; 177020; gene.
DR neXtProt; NX_P24158; -.
DR OpenTargets; ENSG00000196415; -.
DR Orphanet; 900; Granulomatosis with polyangiitis.
DR PharmGKB; PA33842; -.
DR VEuPathDB; HostDB:ENSG00000196415; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT01030000234528; -.
DR HOGENOM; CLU_006842_1_0_1; -.
DR InParanoid; P24158; -.
DR OMA; IQLNRPA; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P24158; -.
DR TreeFam; TF335284; -.
DR BRENDA; 3.4.21.76; 2681.
DR PathwayCommons; P24158; -.
DR Reactome; R-HSA-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-HSA-449836; Other interleukin signaling.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR SABIO-RK; P24158; -.
DR SignaLink; P24158; -.
DR SIGNOR; P24158; -.
DR BioGRID-ORCS; 5657; 11 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; P24158; -.
DR GeneWiki; Proteinase_3; -.
DR GenomeRNAi; 5657; -.
DR Pharos; P24158; Tchem.
DR PRO; PR:P24158; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P24158; protein.
DR Bgee; ENSG00000196415; Expressed in bone marrow and 73 other tissues.
DR ExpressionAtlas; P24158; baseline and differential.
DR Genevisible; P24158; HS.
DR GO; GO:0035578; C:azurophil granule lumen; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0019730; P:antimicrobial humoral response; TAS:Reactome.
DR GO; GO:0045217; P:cell-cell junction maintenance; IMP:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0097029; P:mature conventional dendritic cell differentiation; IDA:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IMP:UniProtKB.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IDA:UniProtKB.
DR GO; GO:0072672; P:neutrophil extravasation; IMP:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Collagen degradation;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Protease; Reference proteome; Secreted; Serine protease; Signal;
KW Zymogen.
FT SIGNAL 1..25
FT PROPEP 26..27
FT /id="PRO_0000027707"
FT CHAIN 28..248
FT /note="Myeloblastin"
FT /evidence="ECO:0000305|PubMed:1688612,
FT ECO:0000305|PubMed:2033050, ECO:0000305|PubMed:2258701,
FT ECO:0000305|PubMed:7897245"
FT /id="PRO_0000027708"
FT PROPEP 249..256
FT /id="PRO_0000027709"
FT DOMAIN 28..248
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 71
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 118
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 203
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8757293,
FT ECO:0007744|PDB:1FUJ"
FT DISULFID 56..72
FT /evidence="ECO:0000269|PubMed:8757293,
FT ECO:0007744|PDB:1FUJ"
FT DISULFID 152..209
FT /evidence="ECO:0000269|PubMed:8757293,
FT ECO:0007744|PDB:1FUJ"
FT DISULFID 182..188
FT /evidence="ECO:0000269|PubMed:8757293,
FT ECO:0007744|PDB:1FUJ"
FT DISULFID 199..224
FT /evidence="ECO:0000269|PubMed:8757293,
FT ECO:0007744|PDB:1FUJ"
FT VARIANT 119
FT /note="V -> I (in dbSNP:rs351111)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1681549, ECO:0000269|PubMed:2377228,
FT ECO:0000269|PubMed:2598267, ECO:0000269|PubMed:7539799,
FT ECO:0000269|PubMed:9924693, ECO:0000269|Ref.3"
FT /id="VAR_011691"
FT VARIANT 135
FT /note="A -> T (in dbSNP:rs1042281)"
FT /evidence="ECO:0000269|PubMed:1400430,
FT ECO:0000269|PubMed:1681549, ECO:0000269|PubMed:2377228,
FT ECO:0000269|PubMed:2598267"
FT /id="VAR_011713"
FT VARIANT 136
FT /note="T -> S (in dbSNP:rs1042282)"
FT /evidence="ECO:0000269|PubMed:1400430,
FT ECO:0000269|PubMed:1681549, ECO:0000269|PubMed:2377228,
FT ECO:0000269|PubMed:2598267"
FT /id="VAR_011714"
FT CONFLICT 2
FT /note="A -> R (in Ref. 9; CAA39203)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="S -> I (in Ref. 19; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="P -> PI (in Ref. 19; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="Q -> E (in Ref. 13; AA sequence and 17; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="R -> A (in Ref. 14; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="S -> D (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="A -> P (in Ref. 1; AAA59558)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="Missing (in Ref. 9; CAA39203)"
FT /evidence="ECO:0000305"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:1FUJ"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:1FUJ"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 98..107
FT /evidence="ECO:0007829|PDB:1FUJ"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 151..160
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 171..178
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 206..209
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:1FUJ"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:1FUJ"
FT HELIX 236..239
FT /evidence="ECO:0007829|PDB:1FUJ"
FT HELIX 240..247
FT /evidence="ECO:0007829|PDB:1FUJ"
SQ SEQUENCE 256 AA; 27807 MW; CBECA36D8C4B2A40 CRC64;
MAHRPPSPAL ASVLLALLLS GAARAAEIVG GHEAQPHSRP YMASLQMRGN PGSHFCGGTL
IHPSFVLTAA HCLRDIPQRL VNVVLGAHNV RTQEPTQQHF SVAQVFLNNY DAENKLNDVL
LIQLSSPANL SASVATVQLP QQDQPVPHGT QCLAMGWGRV GAHDPPAQVL QELNVTVVTF
FCRPHNICTF VPRRKAGICF GDSGGPLICD GIIQGIDSFV IWGCATRLFP DFFTRVALYV
DWIRSTLRRV EAKGRP
