Detail Information for IndEnz0002007689
IED ID IndEnz0002007689
Enzyme Type ID protease007689
Protein Name Myeloblastin
EC 3.4.21.76
AGP7
C-ANCA antigen
Leukocyte proteinase 3
PR-3
PR3
Neutrophil proteinase 4
NP-4
P29
Wegener autoantigen
Gene Name PRTN3 MBN
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MAHRPPSPALASVLLALLLSGAARAAEIVGGHEAQPHSRPYMASLQMRGNPGSHFCGGTLIHPSFVLTAAHCLRDIPQRLVNVVLGAHNVRTQEPTQQHFSVAQVFLNNYDAENKLNDVLLIQLSSPANLSASVATVQLPQQDQPVPHGTQCLAMGWGRVGAHDPPAQVLQELNVTVVTFFCRPHNICTFVPRRKAGICFGDSGGPLICDGIIQGIDSFVIWGCATRLFPDFFTRVALYVDWIRSTLRRVEAKGRP
Enzyme Length 256
Uniprot Accession Number P24158
Absorption
Active Site ACT_SITE 71; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU00274; ACT_SITE 118; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU00274; ACT_SITE 203; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU00274
Activity Regulation ACTIVITY REGULATION: Inhibited by phenylmethanesulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP). {ECO:0000269|PubMed:3198760}.
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-|-Xaa- > -Val-|-Xaa-.; EC=3.4.21.76; Evidence={ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245};
DNA Binding
EC Number 3.4.21.76
Enzyme Function FUNCTION: Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:3198760, PubMed:2033050, PubMed:28240246). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration (PubMed:23202369). May play a role in neutrophil transendothelial migration, probably when associated with CD177 (PubMed:22266279). {ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:23202369, ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:3198760}.
Temperature Dependency
PH Dependency BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.4. {ECO:0000269|PubMed:3198760};
Pathway
nucleotide Binding
Features Active site (3); Beta strand (17); Chain (1); Disulfide bond (4); Domain (1); Erroneous initiation (1); Frameshift (1); Glycosylation (2); Helix (4); Natural variant (3); Propeptide (2); Sequence conflict (9); Signal peptide (1); Turn (1)
Keywords 3D-structure;Cell membrane;Collagen degradation;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Protease;Reference proteome;Secreted;Serine protease;Signal;Zymogen
Interact With P24001-4
Induction INDUCTION: Induced during CSF3/G-CSF-mediated neutrophil differentiation. {ECO:0000269|PubMed:18462208}.
Subcellular Location SUBCELLULAR LOCATION: Cytoplasmic granule {ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245, ECO:0000305|PubMed:17244676}. Secreted {ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:28240246}. Cell membrane {ECO:0000269|PubMed:17244676, ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246}; Peripheral membrane protein {ECO:0000269|PubMed:17244676, ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246}; Extracellular side {ECO:0000269|PubMed:17244676, ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246}. Membrane raft {ECO:0000269|PubMed:21193407}; Peripheral membrane protein {ECO:0000269|PubMed:21193407}; Extracellular side {ECO:0000269|PubMed:21193407}. Note=Localizes predominantly to azurophil granules (primary secretory granules) in neutrophils (PubMed:2033050, PubMed:3198760, PubMed:7897245, PubMed:18462208). Secreted upon neutrophil stimulation by TNF-alpha, lipopolysaccharide (LPS), fMLP and CXCL8/IL8 or during neutrophil transmigration (PubMed:22266279, PubMed:28240246). Following secretion tethered to the cell membrane by CD177 (PubMed:18462208, PubMed:22266279). {ECO:0000269|PubMed:18462208, ECO:0000269|PubMed:2033050, ECO:0000269|PubMed:22266279, ECO:0000269|PubMed:28240246, ECO:0000269|PubMed:3198760, ECO:0000269|PubMed:7897245}.
Modified Residue
Post Translational Modification
Signal Peptide SIGNAL 1..25
Structure 3D X-ray crystallography (1)
Cross Reference PDB 1FUJ;
Mapped Pubmed ID 11035113; 11115080; 11389039; 11714826; 12067299; 12114510; 12135665; 12140766; 12191967; 12200377; 12354776; 12393722; 12444202; 12506139; 12538645; 12832446; 12894870; 12960243; 14525959; 14675038; 15331626; 15527767; 15686586; 15879139; 15916759; 15975933; 16167885; 16263417; 16488976; 16598772; 16792675; 16799473; 17088257; 17158864; 17174955; 17412886; 17452051; 17534941; 17634439; 17681950; 17712045; 17785293; 18021746; 18023421; 18076025; 18596726; 18854317; 19185066; 19447886; 19490915; 19494315; 19913121; 20059480; 20155833; 20412702; 20412704; 20423453; 20491791; 20592714; 20628086; 20828556; 21193404; 21470489; 21700341; 22138257; 22210048; 22270365; 22510451; 22791638; 22810585; 22844112; 22936713; 22952809; 23380137; 23911525; 23957616; 24052258; 24271323; 24291125; 24719228; 24929239; 24949444; 25092677; 25180606; 25416382; 25461407; 25461571; 25788529; 25927497; 26436651; 26873743; 26939803; 26961880; 27559009; 27752292; 27821628; 28029757; 28339364; 28428279; 28546501; 29079698; 29132840; 29621735; 30021768; 30236095; 30880498; 30938436; 31125555; 31490025; 31963828; 31995266; 32303641; 32794199; 33023023; 33679731; 34292081; 8692836;
Motif
Gene Encoded By
Mass 27,807
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda 3.4.21.76;