Full text data of PRTN3
PRTN3
(MBN)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Myeloblastin; 3.4.21.76 (AGP7; C-ANCA antigen; Leukocyte proteinase 3; PR-3; PR3; Neutrophil proteinase 4; NP-4; P29; Wegener autoantigen; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Myeloblastin; 3.4.21.76 (AGP7; C-ANCA antigen; Leukocyte proteinase 3; PR-3; PR3; Neutrophil proteinase 4; NP-4; P29; Wegener autoantigen; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P24158
ID PRTN3_HUMAN Reviewed; 256 AA.
AC P24158; P15637; P18078; Q4VB08; Q4VB09; Q6LBM7; Q6LBN2; Q9UD25;
read moreAC Q9UQD8;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Myeloblastin;
DE EC=3.4.21.76;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Jenne D.E.;
RT "Three human elastase-like genes coordinately expressed in the
RT myelomonocyte lineage are organized as a single genetic locus on
RT 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;
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;
RA Clave E., Molldrem J., Hensel N., Raptis A., Barrett A.J.;
RT "Donor-recipient polymorphism of the proteinase 3 gene: a potential
RT target 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;
RP 156-181 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
RP AND 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
RT arrest 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,
RP VARIANTS ILE-119; THR-135 AND SER-136, AND IDENTITY OF WEGENER'S
RP AUTOANTIGEN WITH 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.
RX PubMed=2033050;
RA Rao N.V., Wehner N.G., Marshall B.C., Gray W.R., Gray B.H.,
RA Hoidal J.R.;
RT "Characterization of proteinase-3 (PR-3), a neutrophil serine
RT proteinase. 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;
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;
RA Ohlsson K., Linder C., Rosengren M.;
RT "Monoclonal antibodies specific for neutrophil proteinase 4.
RT Production and 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;
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.,
RA Marra M.N., 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, AND CATALYTIC ACTIVITY.
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
RT recognize 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.
RT Isolation, characterization, and comparison with T lymphocyte membrane
RT dipeptidylpeptidase IV (CD26).";
RL J. Biol. Chem. 270:14107-14114(1995).
RN [21]
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 [22]
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.,
RA Buerckstuemmer T., 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 [23]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
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
RT of Wegener's granulomatosis antibodies.";
RL J. Mol. Biol. 261:267-278(1996).
CC -!- FUNCTION: Polymorphonuclear leukocyte serine protease that
CC degrades elastin, fibronectin, laminin, vitronectin, and collagen
CC types I, III, and IV (in vitro) and causes emphysema when
CC administered by tracheal insufflation to hamsters.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of proteins, including elastin, by
CC preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Elastase
CC subfamily.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36342.1; Type=Frameshift; Positions=34, 39;
CC Sequence=CAA39598.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Proteinase 3 entry;
CC URL="http://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 PIR; A45080; PRHU3.
DR RefSeq; NP_002768.3; NM_002777.3.
DR UniGene; Hs.928; -.
DR PDB; 1FUJ; X-ray; 2.20 A; A/B/C/D=28-248.
DR PDBsum; 1FUJ; -.
DR ProteinModelPortal; P24158; -.
DR SMR; P24158; 28-248.
DR IntAct; P24158; 2.
DR MINT; MINT-4054660; -.
DR BindingDB; P24158; -.
DR ChEMBL; CHEMBL3900; -.
DR MEROPS; S01.134; -.
DR DMDM; 6174926; -.
DR PaxDb; P24158; -.
DR PeptideAtlas; P24158; -.
DR PRIDE; P24158; -.
DR DNASU; 5657; -.
DR Ensembl; ENST00000234347; ENSP00000234347; ENSG00000196415.
DR GeneID; 5657; -.
DR KEGG; hsa:5657; -.
DR UCSC; uc002lqa.1; human.
DR CTD; 5657; -.
DR GeneCards; GC19P000840; -.
DR HGNC; HGNC:9495; PRTN3.
DR HPA; CAB017558; -.
DR HPA; HPA005938; -.
DR MIM; 177020; gene.
DR neXtProt; NX_P24158; -.
DR Orphanet; 900; Wegener granulomatosis.
DR PharmGKB; PA33842; -.
DR eggNOG; COG5640; -.
DR HOVERGEN; HBG013304; -.
DR InParanoid; P24158; -.
DR KO; K01350; -.
DR OMA; HFSVAQV; -.
DR OrthoDB; EOG7MKW6Q; -.
DR PhylomeDB; P24158; -.
DR BRENDA; 3.4.21.76; 2681.
DR EvolutionaryTrace; P24158; -.
DR GeneWiki; Proteinase_3; -.
DR GenomeRNAi; 5657; -.
DR NextBio; 21988; -.
DR PRO; PR:P24158; -.
DR Bgee; P24158; -.
DR CleanEx; HS_PRTN3; -.
DR Genevestigator; P24158; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008236; F:serine-type peptidase activity; NAS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0097029; P:mature dendritic cell differentiation; IDA:UniProtKB.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR018114; Peptidase_S1_AS.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
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; Collagen degradation; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Polymorphism; Protease; Reference proteome; Serine protease; Signal;
KW Zymogen.
FT SIGNAL 1 25
FT PROPEP 26 27
FT /FTId=PRO_0000027707.
FT CHAIN 28 248 Myeloblastin.
FT /FTId=PRO_0000027708.
FT PROPEP 249 256
FT /FTId=PRO_0000027709.
FT DOMAIN 28 248 Peptidase S1.
FT ACT_SITE 71 71 Charge relay system.
FT ACT_SITE 118 118 Charge relay system.
FT ACT_SITE 203 203 Charge relay system.
FT CARBOHYD 129 129 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 174 174 N-linked (GlcNAc...).
FT DISULFID 56 72
FT DISULFID 152 209
FT DISULFID 182 188
FT DISULFID 199 224
FT VARIANT 119 119 V -> I (in dbSNP:rs351111).
FT /FTId=VAR_011691.
FT VARIANT 135 135 A -> T (in dbSNP:rs1042281).
FT /FTId=VAR_011713.
FT VARIANT 136 136 T -> S (in dbSNP:rs1042282).
FT /FTId=VAR_011714.
FT CONFLICT 2 2 A -> R (in Ref. 9; CAA39203).
FT CONFLICT 38 38 S -> I (in Ref. 19; AA sequence).
FT CONFLICT 40 40 P -> PI (in Ref. 19; AA sequence).
FT CONFLICT 46 46 Q -> E (in Ref. 13; AA sequence and 17;
FT AA sequence).
FT CONFLICT 48 48 R -> A (in Ref. 14; AA sequence).
FT CONFLICT 64 64 S -> D (in Ref. 12; AA sequence).
FT CONFLICT 70 70 A -> P (in Ref. 1; AAA59558).
FT CONFLICT 255 255 Missing (in Ref. 9; CAA39203).
FT STRAND 42 47
FT STRAND 56 62
FT STRAND 65 68
FT HELIX 70 73
FT STRAND 74 76
FT HELIX 78 80
FT STRAND 81 86
FT STRAND 98 107
FT TURN 112 115
FT STRAND 120 126
FT STRAND 151 160
FT STRAND 162 164
FT STRAND 171 178
FT STRAND 186 190
FT STRAND 192 195
FT STRAND 206 209
FT STRAND 212 219
FT STRAND 221 223
FT STRAND 227 229
FT STRAND 231 235
FT HELIX 236 239
FT HELIX 240 247
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
//
ID PRTN3_HUMAN Reviewed; 256 AA.
AC P24158; P15637; P18078; Q4VB08; Q4VB09; Q6LBM7; Q6LBN2; Q9UD25;
read moreAC Q9UQD8;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 22-JAN-2014, entry version 154.
DE RecName: Full=Myeloblastin;
DE EC=3.4.21.76;
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Jenne D.E.;
RT "Three human elastase-like genes coordinately expressed in the
RT myelomonocyte lineage are organized as a single genetic locus on
RT 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;
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;
RA Clave E., Molldrem J., Hensel N., Raptis A., Barrett A.J.;
RT "Donor-recipient polymorphism of the proteinase 3 gene: a potential
RT target 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;
RP 156-181 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
RP AND 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
RT arrest 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,
RP VARIANTS ILE-119; THR-135 AND SER-136, AND IDENTITY OF WEGENER'S
RP AUTOANTIGEN WITH 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.
RX PubMed=2033050;
RA Rao N.V., Wehner N.G., Marshall B.C., Gray W.R., Gray B.H.,
RA Hoidal J.R.;
RT "Characterization of proteinase-3 (PR-3), a neutrophil serine
RT proteinase. 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;
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;
RA Ohlsson K., Linder C., Rosengren M.;
RT "Monoclonal antibodies specific for neutrophil proteinase 4.
RT Production and 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;
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.,
RA Marra M.N., 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, AND CATALYTIC ACTIVITY.
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
RT recognize 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.
RT Isolation, characterization, and comparison with T lymphocyte membrane
RT dipeptidylpeptidase IV (CD26).";
RL J. Biol. Chem. 270:14107-14114(1995).
RN [21]
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 [22]
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.,
RA Buerckstuemmer T., 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 [23]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
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
RT of Wegener's granulomatosis antibodies.";
RL J. Mol. Biol. 261:267-278(1996).
CC -!- FUNCTION: Polymorphonuclear leukocyte serine protease that
CC degrades elastin, fibronectin, laminin, vitronectin, and collagen
CC types I, III, and IV (in vitro) and causes emphysema when
CC administered by tracheal insufflation to hamsters.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of proteins, including elastin, by
CC preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Elastase
CC subfamily.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36342.1; Type=Frameshift; Positions=34, 39;
CC Sequence=CAA39598.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Proteinase 3 entry;
CC URL="http://en.wikipedia.org/wiki/Proteinase_3";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; A45080; PRHU3.
DR RefSeq; NP_002768.3; NM_002777.3.
DR UniGene; Hs.928; -.
DR PDB; 1FUJ; X-ray; 2.20 A; A/B/C/D=28-248.
DR PDBsum; 1FUJ; -.
DR ProteinModelPortal; P24158; -.
DR SMR; P24158; 28-248.
DR IntAct; P24158; 2.
DR MINT; MINT-4054660; -.
DR BindingDB; P24158; -.
DR ChEMBL; CHEMBL3900; -.
DR MEROPS; S01.134; -.
DR DMDM; 6174926; -.
DR PaxDb; P24158; -.
DR PeptideAtlas; P24158; -.
DR PRIDE; P24158; -.
DR DNASU; 5657; -.
DR Ensembl; ENST00000234347; ENSP00000234347; ENSG00000196415.
DR GeneID; 5657; -.
DR KEGG; hsa:5657; -.
DR UCSC; uc002lqa.1; human.
DR CTD; 5657; -.
DR GeneCards; GC19P000840; -.
DR HGNC; HGNC:9495; PRTN3.
DR HPA; CAB017558; -.
DR HPA; HPA005938; -.
DR MIM; 177020; gene.
DR neXtProt; NX_P24158; -.
DR Orphanet; 900; Wegener granulomatosis.
DR PharmGKB; PA33842; -.
DR eggNOG; COG5640; -.
DR HOVERGEN; HBG013304; -.
DR InParanoid; P24158; -.
DR KO; K01350; -.
DR OMA; HFSVAQV; -.
DR OrthoDB; EOG7MKW6Q; -.
DR PhylomeDB; P24158; -.
DR BRENDA; 3.4.21.76; 2681.
DR EvolutionaryTrace; P24158; -.
DR GeneWiki; Proteinase_3; -.
DR GenomeRNAi; 5657; -.
DR NextBio; 21988; -.
DR PRO; PR:P24158; -.
DR Bgee; P24158; -.
DR CleanEx; HS_PRTN3; -.
DR Genevestigator; P24158; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0008236; F:serine-type peptidase activity; NAS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0097029; P:mature dendritic cell differentiation; IDA:UniProtKB.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR018114; Peptidase_S1_AS.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
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; Collagen degradation; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Polymorphism; Protease; Reference proteome; Serine protease; Signal;
KW Zymogen.
FT SIGNAL 1 25
FT PROPEP 26 27
FT /FTId=PRO_0000027707.
FT CHAIN 28 248 Myeloblastin.
FT /FTId=PRO_0000027708.
FT PROPEP 249 256
FT /FTId=PRO_0000027709.
FT DOMAIN 28 248 Peptidase S1.
FT ACT_SITE 71 71 Charge relay system.
FT ACT_SITE 118 118 Charge relay system.
FT ACT_SITE 203 203 Charge relay system.
FT CARBOHYD 129 129 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 174 174 N-linked (GlcNAc...).
FT DISULFID 56 72
FT DISULFID 152 209
FT DISULFID 182 188
FT DISULFID 199 224
FT VARIANT 119 119 V -> I (in dbSNP:rs351111).
FT /FTId=VAR_011691.
FT VARIANT 135 135 A -> T (in dbSNP:rs1042281).
FT /FTId=VAR_011713.
FT VARIANT 136 136 T -> S (in dbSNP:rs1042282).
FT /FTId=VAR_011714.
FT CONFLICT 2 2 A -> R (in Ref. 9; CAA39203).
FT CONFLICT 38 38 S -> I (in Ref. 19; AA sequence).
FT CONFLICT 40 40 P -> PI (in Ref. 19; AA sequence).
FT CONFLICT 46 46 Q -> E (in Ref. 13; AA sequence and 17;
FT AA sequence).
FT CONFLICT 48 48 R -> A (in Ref. 14; AA sequence).
FT CONFLICT 64 64 S -> D (in Ref. 12; AA sequence).
FT CONFLICT 70 70 A -> P (in Ref. 1; AAA59558).
FT CONFLICT 255 255 Missing (in Ref. 9; CAA39203).
FT STRAND 42 47
FT STRAND 56 62
FT STRAND 65 68
FT HELIX 70 73
FT STRAND 74 76
FT HELIX 78 80
FT STRAND 81 86
FT STRAND 98 107
FT TURN 112 115
FT STRAND 120 126
FT STRAND 151 160
FT STRAND 162 164
FT STRAND 171 178
FT STRAND 186 190
FT STRAND 192 195
FT STRAND 206 209
FT STRAND 212 219
FT STRAND 221 223
FT STRAND 227 229
FT STRAND 231 235
FT HELIX 236 239
FT HELIX 240 247
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
//
MIM
177020
*RECORD*
*FIELD* NO
177020
*FIELD* TI
*177020 PROTEINASE 3; PRTN3
;;PR3;;
MYELOBLASTIN; MBT;;
WEGENER AUTOANTIGEN; P29;;
read moreAZUROPHIL GRANULE PROTEIN 7; AGP7;;
SERINE PROTEINASE, NEUTROPHIL
*FIELD* TX
CLONING
Wegener granulomatosis (608710) is a disease of unknown cause and
pathogenesis. Its major features are necrotizing granulomatous lesions,
which most often affect the upper and lower airways and are associated
with vasculitis, necrotizing glomerulonephritis, and pulmonary
capillaritis. It is a devastating illness; without immunosuppressive
therapy, over 80% of patients die within 1 year, often because of rapid
loss of renal function or massive pulmonary hemorrhage. Definitive
diagnosis hitherto depended on demonstration of characteristic
histologic findings. Beginning with the report of Davies et al. (1982),
detection of antineutrophil antibodies provided an immunologic
diagnosis. Niles et al. (1989) demonstrated that the circulating IgG
autoantibodies that produced a cytoplasmic pattern of staining in
neutrophils from 10 patients with Wegener granulomatosis reacted, in
Western blot analysis, with a 29-kD neutrophil protein (P29) that has
the characteristics of a distinctive serine proteinase. Ludemann et al.
(1990) showed further that the P29 antigen is identical to proteinase-3
(PR3). The neutral serine protease PR3 was isolated, identified, and
characterized from polymorphonuclear leukocytes by Kao et al. (1988).
Jenne et al. (1990) confirmed the identity of proteinase-3 and P29 and
showed that it is identical also to so-called AGP7, a novel neutrophil
serine protease of azurophil granules. Furthermore, they showed that
proteinase-3 is identical to myeloblastin, which has antiproliferative
properties. Gupta et al. (1990) corroborated the identity of the Wegener
autoantigen with cloned myeloblastin.
Zimmer et al. (1992) determined that proteinase-3 is one of the
antibiotic proteins of neutrophilic granules belonging to the serine
protease family. It is closely related to 2 others, neutrophil elastase
(ELA2; 130130) and azurocidin (AZU; 162815), and all 3 of these genes
are located in a cluster on chromosome 19. All 3 genes are expressed
coordinately and their protein products are packaged together into
azurophil granules during neutrophil differentiation.
Northern analysis by Sturrock et al. (1992) suggested that expression of
the PRTN3 gene is primarily confined to the promyelocytic/myelocytic
stage of bone marrow development.
GENE FUNCTION
Kao et al. (1988) showed that PR3 has an ability to induce emphysema in
hamsters commensurate with that of leukocyte elastase.
Ludemann et al. (1990) showed that PR3 is a neutral serine protease that
is able to cleave elastin.
Lutz et al. (2000) showed that myeloblastin is expressed specifically in
immature myeloid cells, that myeloblastin is a granulocyte
colony-stimulating factor (G-CSF)-responsive gene, and that its
constitutive overexpression confers factor-independent growth to Ba/F3
cells expressing the G-CFS receptor. Lutz et al. (2000) suggested that
their results point to myeloblastin as a G-CSF-responsive gene critical
to factor-independent growth and indicate that the expression of the
G-CSF receptor is a prerequisite to this process. A 91-bp myeloblastin
promoter region containing binding sites for PU.1 (165170), C/EBP
(116897), and c-Myb (189990) is responsive to G-CSF treatment. Although
PU.1, C/EBP, and c-Myb transcription factors all were critical for
expression of myeloblastin, its upregulation by G-CSF was associated
mainly with PU.1. Lutz et al. (2000) concluded that myeloblastin is an
important target of PU.1 and a key protease for factor-independent
growth of hematopoietic cells.
Using RT-PCR, immunoblot, and immunofluorescence microscopy analyses,
Sugawara et al. (2001) demonstrated that oral epithelial cells express
IL18 (600953) mRNA and the 24-kD IL18 precursor protein. ELISA analysis
showed that stimulation of the cells with PRTN3 and lipopolysaccharide
(LPS) after gamma-interferon (IFNG; 147570) priming leads to
intracellular production and secretion of the 18-kD bioactive form of
IL18 in a caspase-1 (CASP1; 147678)-independent fashion. Cell
fractionation and immunoblot analyses indicated that PRTN3 acts on the
cell surface after the IFNG priming, not intracellularly. Sugawara et
al. (2001) proposed that PRTN3 together with LPS and IFNG may be
involved in mucosal inflammation, such as periodontitis.
Patients with inflammatory vascular disease caused by antineutrophil
cytoplasmic autoantibodies (ANCA) with specificity for proteinase-3
harbor not only antibodies to the autoantigen (PR3), but also antibodies
to a peptide translated from the antisense DNA strand of PR3
(complementary PR3, or cPR3) or to a mimic of this peptide. Pendergraft
et al. (2004) showed that immunization of mice with the middle region of
cPR3 resulted in production of antibodies not only to cPR3, but also to
the immunogen's sense peptide counterpart, PR3. Both human and mouse
antibodies to PR3 and cPR3 bound to each other, indicating idiotypic
relationships. Pendergraft et al. (2004) concluded that autoimmunity can
be initiated through an immune response against a peptide that is
antisense or complementary to the autoantigen, which then induces
antiidiotypic antibodies (autoantibodies) that crossreact with the
autoantigen.
Using IL32-alpha (606001) in agarose ligand affinity chromatography
analysis of concentrated urinary proteins, Novick et al. (2006) isolated
a 30-kD protein they identified as PR3. Surface plasmon resonance
analysis showed that urinary and neutrophil PR3 had similar binding
affinities for IL32-alpha, and IL32-alpha binding did not require PR3
enzymatic activity. However, limited PR3-mediated cleavage of IL32-alpha
resulted in stronger induction of Mip2 (CXCL2; 139110) in murine
macrophages and IL8 (146930) in human mononuclear cells. Novick et al.
(2006) proposed that inhibition of PR3 activity or IL32 neutralization
by inactive PR3 may reduce the consequences of IL32 activity in
immune-regulated diseases.
GENE STRUCTURE
Zimmer et al. (1992) determined that the PR3 gene has 5 exons. Sturrock
et al. (1992) showed that the PRTN3 gene spans about 6.5 kb and
comprises 5 exons and 4 introns.
MAPPING
Zimmer et al. (1992) mapped the PR3, ELA2, and AZU gene cluster to the
tip of the short arm of chromosome 19. By PCR amplification of the PRTN3
gene from a human/hamster hybrid cell line, Sturrock et al. (1992)
localized it to human chromosome 19. Sturrock et al. (1993) used
fluorescence in situ hybridization to localize the PRTN3 gene to
19p13.3.
By interspecific backcross analysis, Belaaouaj et al. (1997) mapped the
mouse Pr3 gene to chromosome 10.
*FIELD* SA
Campanelli et al. (1990)
*FIELD* RF
1. Belaaouaj, A.; Walsh, B. C.; Jenkins, N. A.; Copeland, N. G.; Shapiro,
S. D.: Characterization of the mouse neutrophil elastase gene and
localization to chromosome 10. Mammalian Genome 8: 5-8, 1997.
2. Campanelli, D.; Melchior, M.; Fu, Y.; Nakata, M.; Shuman, H.; Nathan,
C.; Gabay, J. E.: Cloning of cDNA for proteinase 3: a serine protease,
antibiotic, and autoantigen from human neutrophils. J. Exp. Med. 172:
1709-1715, 1990.
3. Davies, D. J.; Moran, J. E.; Niall, J. F.; Ryan, G. B.: Segmental
necrotising glomerulonephritis with antineutrophil antibody: possible
arbovirus aetiology. Brit. Med. J. 285: 606 only, 1982.
4. Gupta, S. K.; Niles, J. L.; McCluskey, R. T.; Arnaout, M. A.:
Identity of Wegener's autoantigen (P29) with proteinase 3 and myeloblastin.
(Letter) Blood 76: 2162 only, 1990.
5. Jenne, D. E.; Tschopp, J.; Ludemann, J.; Utecht, B.; Gross, W.
L.: Wegener's autoantigen decoded. (Letter) Nature 346: 520 only,
1990.
6. Kao, R. C.; Wehner, N. G.; Skubitz, K. M.; Gray, B. H.; Hoidal,
J. R.: Proteinase 3: a distinct human polymorphonuclear leukocyte
proteinase that produces emphysema in hamsters. J. Clin. Invest. 82:
1963-1973, 1988.
7. Ludemann, J.; Utecht, B.; Gross, W. L.: Anti-neutrophil cytoplasm
antibodies in Wegener's granulomatosis recognize an elastinolytic
enzyme. J. Exp. Med. 171: 357-362, 1990.
8. Lutz, P. G.; Moog-Lutz, C.; Coumau-Gatbois, E.; Kobari, L.; Di
Gioia, Y.; Cayre, Y. E.: Myeloblastin is a granulocyte colony-stimulating
factor-responsive gene conferring factor-independent growth to hematopoietic
cells. Proc. Nat. Acad. Sci. 97: 1601-1606, 2000.
9. Niles, J. L.; McCluskey, R. T.; Ahmad, M. F.; Arnaout, M. A.:
Wegener's granulomatosis autoantigen is a novel neutrophil serine
proteinase. Blood 74: 1888-1893, 1989.
10. Novick, D.; Rubinstein, M.; Azam, T.; Rabinkov, A.; Dinarello,
C. A.; Kim, S.-H.: Proteinase 3 is an IL-32 binding protein. Proc.
Nat. Acad. Sci. 103: 3316-3321, 2006.
11. Pendergraft, W. F., III; Preston, G. A.; Shah, R. R.; Tropsha,
A.; Carter, C. W., Jr.; Jennette, J. C.; Falk, R. J.: Autoimmunity
is triggered by cPR-3(105-201), a protein complementary to human autoantigen
proteinase-3. Nature Med. 10: 72-79, 2004.
12. Sturrock, A. B.; Espinosa, R., III; Hoidal, J. R.; Le Beau, M.
M.: Localization of the gene encoding proteinase-3 (the Wegener's
granulomatosis autoantigen) to human chromosome band 19p13.3. Cytogenet.
Cell Genet. 64: 33-34, 1993.
13. Sturrock, A. B.; Franklin, K. F.; Rao, G.; Marshall, B. C.; Rebentisch,
M. B.; Lemons, R. S.; Hoidal, J. R.: Structure, chromosomal assignment,
and expression of the gene for proteinase-3: the Wegener's granulomatosis
autoantigen. J. Biol. Chem. 267: 21193-21199, 1992.
14. Sugawara, S.; Uehara, A.; Nochi, T.; Yamaguchi, T.; Ueda, H.;
Sugiyama, A.; Hanzawa, K.; Kumagai, K.; Okamura, H.; Takada, H.:
Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion
by human oral epithelial cells. J. Immun. 167: 6568-6575, 2001.
15. Zimmer, M.; Medcalf, R. L.; Fink, T. M.; Mattmann, C.; Lichter,
P.; Jenne, D. E.: Three human elastase-like genes coordinately expressed
in the myelomonocyte lineage are organized as a single genetic locus
on 19pter. Proc. Nat. Acad. Sci. 89: 8215-8219, 1992.
*FIELD* CN
Paul J. Converse - updated: 3/24/2006
Ada Hamosh - updated: 12/16/2003
Paul J. Converse - updated: 2/20/2002
Ada Hamosh - updated: 6/9/2000
Carol A. Bocchini - updated: 6/14/1999
Alan F. Scott - updated: 8/15/1996
*FIELD* CD
Victor A. McKusick: 1/3/1989
*FIELD* ED
mgross: 03/29/2006
mgross: 3/29/2006
terry: 3/24/2006
mgross: 6/4/2004
alopez: 2/17/2004
alopez: 12/17/2003
terry: 12/16/2003
mgross: 2/20/2002
carol: 11/21/2000
alopez: 6/16/2000
terry: 6/9/2000
carol: 6/14/1999
alopez: 11/2/1998
mark: 8/19/1996
terry: 8/15/1996
mimadm: 2/25/1995
carol: 9/15/1993
carol: 4/2/1993
carol: 11/20/1992
carol: 11/9/1992
carol: 9/29/1992
*RECORD*
*FIELD* NO
177020
*FIELD* TI
*177020 PROTEINASE 3; PRTN3
;;PR3;;
MYELOBLASTIN; MBT;;
WEGENER AUTOANTIGEN; P29;;
read moreAZUROPHIL GRANULE PROTEIN 7; AGP7;;
SERINE PROTEINASE, NEUTROPHIL
*FIELD* TX
CLONING
Wegener granulomatosis (608710) is a disease of unknown cause and
pathogenesis. Its major features are necrotizing granulomatous lesions,
which most often affect the upper and lower airways and are associated
with vasculitis, necrotizing glomerulonephritis, and pulmonary
capillaritis. It is a devastating illness; without immunosuppressive
therapy, over 80% of patients die within 1 year, often because of rapid
loss of renal function or massive pulmonary hemorrhage. Definitive
diagnosis hitherto depended on demonstration of characteristic
histologic findings. Beginning with the report of Davies et al. (1982),
detection of antineutrophil antibodies provided an immunologic
diagnosis. Niles et al. (1989) demonstrated that the circulating IgG
autoantibodies that produced a cytoplasmic pattern of staining in
neutrophils from 10 patients with Wegener granulomatosis reacted, in
Western blot analysis, with a 29-kD neutrophil protein (P29) that has
the characteristics of a distinctive serine proteinase. Ludemann et al.
(1990) showed further that the P29 antigen is identical to proteinase-3
(PR3). The neutral serine protease PR3 was isolated, identified, and
characterized from polymorphonuclear leukocytes by Kao et al. (1988).
Jenne et al. (1990) confirmed the identity of proteinase-3 and P29 and
showed that it is identical also to so-called AGP7, a novel neutrophil
serine protease of azurophil granules. Furthermore, they showed that
proteinase-3 is identical to myeloblastin, which has antiproliferative
properties. Gupta et al. (1990) corroborated the identity of the Wegener
autoantigen with cloned myeloblastin.
Zimmer et al. (1992) determined that proteinase-3 is one of the
antibiotic proteins of neutrophilic granules belonging to the serine
protease family. It is closely related to 2 others, neutrophil elastase
(ELA2; 130130) and azurocidin (AZU; 162815), and all 3 of these genes
are located in a cluster on chromosome 19. All 3 genes are expressed
coordinately and their protein products are packaged together into
azurophil granules during neutrophil differentiation.
Northern analysis by Sturrock et al. (1992) suggested that expression of
the PRTN3 gene is primarily confined to the promyelocytic/myelocytic
stage of bone marrow development.
GENE FUNCTION
Kao et al. (1988) showed that PR3 has an ability to induce emphysema in
hamsters commensurate with that of leukocyte elastase.
Ludemann et al. (1990) showed that PR3 is a neutral serine protease that
is able to cleave elastin.
Lutz et al. (2000) showed that myeloblastin is expressed specifically in
immature myeloid cells, that myeloblastin is a granulocyte
colony-stimulating factor (G-CSF)-responsive gene, and that its
constitutive overexpression confers factor-independent growth to Ba/F3
cells expressing the G-CFS receptor. Lutz et al. (2000) suggested that
their results point to myeloblastin as a G-CSF-responsive gene critical
to factor-independent growth and indicate that the expression of the
G-CSF receptor is a prerequisite to this process. A 91-bp myeloblastin
promoter region containing binding sites for PU.1 (165170), C/EBP
(116897), and c-Myb (189990) is responsive to G-CSF treatment. Although
PU.1, C/EBP, and c-Myb transcription factors all were critical for
expression of myeloblastin, its upregulation by G-CSF was associated
mainly with PU.1. Lutz et al. (2000) concluded that myeloblastin is an
important target of PU.1 and a key protease for factor-independent
growth of hematopoietic cells.
Using RT-PCR, immunoblot, and immunofluorescence microscopy analyses,
Sugawara et al. (2001) demonstrated that oral epithelial cells express
IL18 (600953) mRNA and the 24-kD IL18 precursor protein. ELISA analysis
showed that stimulation of the cells with PRTN3 and lipopolysaccharide
(LPS) after gamma-interferon (IFNG; 147570) priming leads to
intracellular production and secretion of the 18-kD bioactive form of
IL18 in a caspase-1 (CASP1; 147678)-independent fashion. Cell
fractionation and immunoblot analyses indicated that PRTN3 acts on the
cell surface after the IFNG priming, not intracellularly. Sugawara et
al. (2001) proposed that PRTN3 together with LPS and IFNG may be
involved in mucosal inflammation, such as periodontitis.
Patients with inflammatory vascular disease caused by antineutrophil
cytoplasmic autoantibodies (ANCA) with specificity for proteinase-3
harbor not only antibodies to the autoantigen (PR3), but also antibodies
to a peptide translated from the antisense DNA strand of PR3
(complementary PR3, or cPR3) or to a mimic of this peptide. Pendergraft
et al. (2004) showed that immunization of mice with the middle region of
cPR3 resulted in production of antibodies not only to cPR3, but also to
the immunogen's sense peptide counterpart, PR3. Both human and mouse
antibodies to PR3 and cPR3 bound to each other, indicating idiotypic
relationships. Pendergraft et al. (2004) concluded that autoimmunity can
be initiated through an immune response against a peptide that is
antisense or complementary to the autoantigen, which then induces
antiidiotypic antibodies (autoantibodies) that crossreact with the
autoantigen.
Using IL32-alpha (606001) in agarose ligand affinity chromatography
analysis of concentrated urinary proteins, Novick et al. (2006) isolated
a 30-kD protein they identified as PR3. Surface plasmon resonance
analysis showed that urinary and neutrophil PR3 had similar binding
affinities for IL32-alpha, and IL32-alpha binding did not require PR3
enzymatic activity. However, limited PR3-mediated cleavage of IL32-alpha
resulted in stronger induction of Mip2 (CXCL2; 139110) in murine
macrophages and IL8 (146930) in human mononuclear cells. Novick et al.
(2006) proposed that inhibition of PR3 activity or IL32 neutralization
by inactive PR3 may reduce the consequences of IL32 activity in
immune-regulated diseases.
GENE STRUCTURE
Zimmer et al. (1992) determined that the PR3 gene has 5 exons. Sturrock
et al. (1992) showed that the PRTN3 gene spans about 6.5 kb and
comprises 5 exons and 4 introns.
MAPPING
Zimmer et al. (1992) mapped the PR3, ELA2, and AZU gene cluster to the
tip of the short arm of chromosome 19. By PCR amplification of the PRTN3
gene from a human/hamster hybrid cell line, Sturrock et al. (1992)
localized it to human chromosome 19. Sturrock et al. (1993) used
fluorescence in situ hybridization to localize the PRTN3 gene to
19p13.3.
By interspecific backcross analysis, Belaaouaj et al. (1997) mapped the
mouse Pr3 gene to chromosome 10.
*FIELD* SA
Campanelli et al. (1990)
*FIELD* RF
1. Belaaouaj, A.; Walsh, B. C.; Jenkins, N. A.; Copeland, N. G.; Shapiro,
S. D.: Characterization of the mouse neutrophil elastase gene and
localization to chromosome 10. Mammalian Genome 8: 5-8, 1997.
2. Campanelli, D.; Melchior, M.; Fu, Y.; Nakata, M.; Shuman, H.; Nathan,
C.; Gabay, J. E.: Cloning of cDNA for proteinase 3: a serine protease,
antibiotic, and autoantigen from human neutrophils. J. Exp. Med. 172:
1709-1715, 1990.
3. Davies, D. J.; Moran, J. E.; Niall, J. F.; Ryan, G. B.: Segmental
necrotising glomerulonephritis with antineutrophil antibody: possible
arbovirus aetiology. Brit. Med. J. 285: 606 only, 1982.
4. Gupta, S. K.; Niles, J. L.; McCluskey, R. T.; Arnaout, M. A.:
Identity of Wegener's autoantigen (P29) with proteinase 3 and myeloblastin.
(Letter) Blood 76: 2162 only, 1990.
5. Jenne, D. E.; Tschopp, J.; Ludemann, J.; Utecht, B.; Gross, W.
L.: Wegener's autoantigen decoded. (Letter) Nature 346: 520 only,
1990.
6. Kao, R. C.; Wehner, N. G.; Skubitz, K. M.; Gray, B. H.; Hoidal,
J. R.: Proteinase 3: a distinct human polymorphonuclear leukocyte
proteinase that produces emphysema in hamsters. J. Clin. Invest. 82:
1963-1973, 1988.
7. Ludemann, J.; Utecht, B.; Gross, W. L.: Anti-neutrophil cytoplasm
antibodies in Wegener's granulomatosis recognize an elastinolytic
enzyme. J. Exp. Med. 171: 357-362, 1990.
8. Lutz, P. G.; Moog-Lutz, C.; Coumau-Gatbois, E.; Kobari, L.; Di
Gioia, Y.; Cayre, Y. E.: Myeloblastin is a granulocyte colony-stimulating
factor-responsive gene conferring factor-independent growth to hematopoietic
cells. Proc. Nat. Acad. Sci. 97: 1601-1606, 2000.
9. Niles, J. L.; McCluskey, R. T.; Ahmad, M. F.; Arnaout, M. A.:
Wegener's granulomatosis autoantigen is a novel neutrophil serine
proteinase. Blood 74: 1888-1893, 1989.
10. Novick, D.; Rubinstein, M.; Azam, T.; Rabinkov, A.; Dinarello,
C. A.; Kim, S.-H.: Proteinase 3 is an IL-32 binding protein. Proc.
Nat. Acad. Sci. 103: 3316-3321, 2006.
11. Pendergraft, W. F., III; Preston, G. A.; Shah, R. R.; Tropsha,
A.; Carter, C. W., Jr.; Jennette, J. C.; Falk, R. J.: Autoimmunity
is triggered by cPR-3(105-201), a protein complementary to human autoantigen
proteinase-3. Nature Med. 10: 72-79, 2004.
12. Sturrock, A. B.; Espinosa, R., III; Hoidal, J. R.; Le Beau, M.
M.: Localization of the gene encoding proteinase-3 (the Wegener's
granulomatosis autoantigen) to human chromosome band 19p13.3. Cytogenet.
Cell Genet. 64: 33-34, 1993.
13. Sturrock, A. B.; Franklin, K. F.; Rao, G.; Marshall, B. C.; Rebentisch,
M. B.; Lemons, R. S.; Hoidal, J. R.: Structure, chromosomal assignment,
and expression of the gene for proteinase-3: the Wegener's granulomatosis
autoantigen. J. Biol. Chem. 267: 21193-21199, 1992.
14. Sugawara, S.; Uehara, A.; Nochi, T.; Yamaguchi, T.; Ueda, H.;
Sugiyama, A.; Hanzawa, K.; Kumagai, K.; Okamura, H.; Takada, H.:
Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion
by human oral epithelial cells. J. Immun. 167: 6568-6575, 2001.
15. Zimmer, M.; Medcalf, R. L.; Fink, T. M.; Mattmann, C.; Lichter,
P.; Jenne, D. E.: Three human elastase-like genes coordinately expressed
in the myelomonocyte lineage are organized as a single genetic locus
on 19pter. Proc. Nat. Acad. Sci. 89: 8215-8219, 1992.
*FIELD* CN
Paul J. Converse - updated: 3/24/2006
Ada Hamosh - updated: 12/16/2003
Paul J. Converse - updated: 2/20/2002
Ada Hamosh - updated: 6/9/2000
Carol A. Bocchini - updated: 6/14/1999
Alan F. Scott - updated: 8/15/1996
*FIELD* CD
Victor A. McKusick: 1/3/1989
*FIELD* ED
mgross: 03/29/2006
mgross: 3/29/2006
terry: 3/24/2006
mgross: 6/4/2004
alopez: 2/17/2004
alopez: 12/17/2003
terry: 12/16/2003
mgross: 2/20/2002
carol: 11/21/2000
alopez: 6/16/2000
terry: 6/9/2000
carol: 6/14/1999
alopez: 11/2/1998
mark: 8/19/1996
terry: 8/15/1996
mimadm: 2/25/1995
carol: 9/15/1993
carol: 4/2/1993
carol: 11/20/1992
carol: 11/9/1992
carol: 9/29/1992