PRTN3_MOUSE
ID PRTN3_MOUSE Reviewed; 254 AA.
AC Q61096; O08809;
DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1999, sequence version 2.
DT 25-MAY-2022, entry version 147.
DE RecName: Full=Myeloblastin;
DE EC=3.4.21.76;
DE AltName: Full=Proteinase 3;
DE Short=PR-3;
DE Flags: Precursor;
GN Name=Prtn3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=9925946; DOI=10.1159/000015144;
RA Sturrock A., Franklin K.F., Wu S.-Q., Hoidal J.R.;
RT "Characterization and localization of the genes for mouse proteinase-3
RT (Prtn3) and neutrophil elastase (Ela2).";
RL Cytogenet. Cell Genet. 83:104-108(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv;
RX PubMed=9187364; DOI=10.1016/s0014-5793(97)00418-3;
RA Jenne D.E., Froehlich L., Hummel A.M., Specks U.;
RT "Cloning and functional expression of the murine homologue of proteinase 3:
RT implications for the design of murine models of vasculitis.";
RL FEBS Lett. 408:187-190(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-254.
RC STRAIN=BALB/cJ;
RX PubMed=9211743; DOI=10.1007/s002510050260;
RA Aveskogh M., Lutzelschwab C., Huang M.R., Hellman L.;
RT "Characterization of cDNA clones encoding mouse proteinase 3
RT (myeloblastine) and cathepsin G.";
RL Immunogenetics 46:181-191(1997).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Serine protease that degrades elastin, fibronectin, laminin,
CC vitronectin, and collagen types I, III, and IV (in vitro). By cleaving
CC and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier
CC function and thus vascular integrity during neutrophil transendothelial
CC migration. May play a role in neutrophil transendothelial migration,
CC probably when associated with CD177. {ECO:0000250|UniProtKB:P24158}.
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:0000250|UniProtKB:P24158};
CC -!- SUBUNIT: May form dimers. Interacts with CD177; the interaction tethers
CC PRTN3 to the cell surface; the interaction is direct. Interacts with
CC SERPINB1. {ECO:0000250|UniProtKB:P24158}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P24158}. Secreted
CC {ECO:0000250|UniProtKB:P24158}. Cell membrane
CC {ECO:0000250|UniProtKB:P24158}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P24158}; Extracellular side
CC {ECO:0000250|UniProtKB:P24158}. Membrane raft
CC {ECO:0000250|UniProtKB:P24158}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P24158}; Extracellular side
CC {ECO:0000250|UniProtKB:P24158}. Note=Localizes predominantly to
CC azurophil granules (primary secretory granules) in neutrophils.
CC Secreted upon neutrophil stimulation by TNF-alpha, lipopolysaccharide
CC (LPS), fMLP and CXCL8/IL8 or during neutrophil transmigration.
CC Following secretion tethered to the cell membrane by CD177.
CC {ECO:0000250|UniProtKB:P24158}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Elastase subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; AF082186; AAC79701.1; -; Genomic_DNA.
DR EMBL; U97073; AAB58055.1; -; mRNA.
DR EMBL; U43525; AAB67271.1; -; mRNA.
DR CCDS; CCDS23993.1; -.
DR RefSeq; NP_035308.2; NM_011178.2.
DR AlphaFoldDB; Q61096; -.
DR SMR; Q61096; -.
DR STRING; 10090.ENSMUSP00000006679; -.
DR BindingDB; Q61096; -.
DR ChEMBL; CHEMBL5384; -.
DR MEROPS; S01.134; -.
DR GlyGen; Q61096; 2 sites.
DR CPTAC; non-CPTAC-3494; -.
DR MaxQB; Q61096; -.
DR PaxDb; Q61096; -.
DR PeptideAtlas; Q61096; -.
DR PRIDE; Q61096; -.
DR ProteomicsDB; 291826; -.
DR DNASU; 19152; -.
DR GeneID; 19152; -.
DR KEGG; mmu:19152; -.
DR UCSC; uc007gah.1; mouse.
DR CTD; 5657; -.
DR MGI; MGI:893580; Prtn3.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; Q61096; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; Q61096; -.
DR TreeFam; TF335284; -.
DR BRENDA; 3.4.21.76; 3474.
DR Reactome; R-MMU-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-6803157; Antimicrobial peptides.
DR BioGRID-ORCS; 19152; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Prtn3; mouse.
DR PRO; PR:Q61096; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q61096; protein.
DR GO; GO:0035578; C:azurophil granule lumen; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0044853; C:plasma membrane raft; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0045217; P:cell-cell junction maintenance; ISO:MGI.
DR GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0097029; P:mature conventional dendritic cell differentiation; ISO:MGI.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0050765; P:negative regulation of phagocytosis; ISO:MGI.
DR GO; GO:0072672; P:neutrophil extravasation; ISO:MGI.
DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
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 Cell membrane; Collagen degradation; Disulfide bond; Glycoprotein;
KW Hydrolase; Lysosome; Membrane; Protease; Reference proteome; Secreted;
KW Serine protease; Signal; Zymogen.
FT SIGNAL 1..27
FT /evidence="ECO:0000250"
FT PROPEP 28..29
FT /evidence="ECO:0000250"
FT /id="PRO_0000027710"
FT CHAIN 30..250
FT /note="Myeloblastin"
FT /id="PRO_0000027711"
FT PROPEP 251..254
FT /evidence="ECO:0000250"
FT /id="PRO_0000027712"
FT DOMAIN 30..250
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 73
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 120
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 205
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 58..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 154..211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 184..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 201..226
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CONFLICT 2
FT /note="S -> A (in Ref. 2; AAB58055)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 254 AA; 27626 MW; 00CEB989A3CB79CA CRC64;
MSGSYPSPKG IHPFLLLALV VGGAVQASKI VGGHEARPHS RPYVASLQLS RFPGSHFCGG
TLIHPRFVLT AAHCLQDISW QLVTVVLGAH DLLSSEPEQQ KFTISQVFQN NYNPEENLND
VLLLQLNRTA SLGKEVAVAS LPQQDQTLSQ GTQCLAMGWG RLGTQAPTPR VLQELNVTVV
TFLCREHNVC TLVPRRAAGI CFGDSGGPLI CNGILHGVDS FVIRECASLQ FPDFFARVSM
YVDWIQNVLR GAEP
