IED Industry Enzyme Database

Detail Information for IndEnz0002003435
IED ID IndEnz0002003435
Enzyme Type ID protease003435
Protein Name Natriuretic peptides B
Brain natriuretic factor prohormone
preproBNP
proBNP
Gamma-brain natriuretic peptide
Iso-ANP

Cleaved into: NT-proBNP
NT-pro-BNP
NT-proBNP
1-76
; proBNP
3-108
; Brain natriuretic peptide 32
BNP
1-32
BNP-32
Brain natriuretic peptide
BNP
; BNP
1-30
; BNP
1-29
; BNP
1-28
; BNP
2-31
; BNP
3-32
des-SerPro-BNP
proBNP
79-108
; BNP
3-30
; BNP
3-29
; Brain natriuretic peptide 29
BNP
4-32
; BNP
4-31
; BNP
4-30
; BNP
4-29
; BNP
4-27
; BNP
5-32
; BNP
5-31
; BNP
5-29
Gene Name NPPB
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 MDPQTAPSRALLLLLFLHLAFLGGRSHPLGSPGSASDLETSGLQEQRNHLQGKLSELQVEQTSLEPLQESPRPTGVWKSREVATEGIRGHRKMVLYTLRAPRSPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH
Enzyme Length 134
Uniprot Accession Number P16860
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: [Brain natriuretic peptide 32]: Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:9458824, PubMed:1672777, PubMed:1914098, PubMed:17372040). May also function as a paracrine antifibrotic factor in the heart (By similarity). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins that drive various biological responses (PubMed:9458824, PubMed:1672777, PubMed:17372040, PubMed:21098034, PubMed:17349887, PubMed:25339504). Involved in regulating the extracellular fluid volume and maintaining the fluid-electrolyte balance through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion (PubMed:9458824, PubMed:1914098). Binds the clearance receptor NPR3 (PubMed:16870210). {ECO:0000250|UniProtKB:P40753, ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:16870210, ECO:0000269|PubMed:17349887, ECO:0000269|PubMed:17372040, ECO:0000269|PubMed:1914098, ECO:0000269|PubMed:21098034, ECO:0000269|PubMed:25339504, ECO:0000269|PubMed:9458824}.; FUNCTION: [NT-proBNP]: May affect cardio-renal homeostasis (PubMed:17372040). Able to promote the production of cGMP although its potency is very low compared to brain natriuretic peptide 32 (PubMed:17372040). {ECO:0000269|PubMed:17372040}.; FUNCTION: [BNP(3-32)]: May have a role in cardio-renal homeostasis (PubMed:17372040). Able to promote the production of cGMP (PubMed:17372040). {ECO:0000269|PubMed:17372040}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Beta strand (1); Chain (1); Disulfide bond (1); Frameshift (1); Glycosylation (7); Mutagenesis (4); Natural variant (3); Peptide (18); Signal peptide (1); Site (4)
Keywords 3D-structure;Direct protein sequencing;Disulfide bond;Glycoprotein;Hormone;Pharmaceutical;Reference proteome;Secreted;Signal;Vasoactive;Vasodilator
Interact With A8MQ03; P57678; Q6A162; P60411; Q7Z3S9; P25788; Q9UJW9
Induction
Subcellular Location SUBCELLULAR LOCATION: [NT-proBNP]: Secreted {ECO:0000269|PubMed:18466803, ECO:0000269|PubMed:25339504}. Note=Detected in blood. {ECO:0000269|PubMed:18466803, ECO:0000269|PubMed:25339504}.; SUBCELLULAR LOCATION: [proBNP(3-108)]: Secreted {ECO:0000269|PubMed:17367664}. Note=Detected in blood. {ECO:0000269|PubMed:17367664}.; SUBCELLULAR LOCATION: [Brain natriuretic peptide 32]: Secreted {ECO:0000269|PubMed:17367664, ECO:0000269|PubMed:18466803, ECO:0000269|PubMed:1914098, ECO:0000269|PubMed:25339504}. Note=Detected in blood. {ECO:0000269|PubMed:17367664, ECO:0000269|PubMed:18466803, ECO:0000269|PubMed:1914098, ECO:0000269|PubMed:25339504}.; SUBCELLULAR LOCATION: [BNP(3-32)]: Secreted {ECO:0000269|PubMed:17367664}. Note=Detected in blood. {ECO:0000269|PubMed:17367664}.
Modified Residue
Post Translational Modification PTM: The precursor molecule is proteolytically cleaved by the endoproteases FURIN or CORIN at Arg-102 to produce brain natriuretic peptide 32 and NT-proBNP (PubMed:21314817, PubMed:10880574, PubMed:21763278, PubMed:20489134, PubMed:21482747). This likely occurs after it has been secreted into the blood, either during circulation or in the target cells (PubMed:21482747). CORIN also cleaves the precursor molecule at additional residues including Arg-99 and possibly Lys-105 (PubMed:20489134, PubMed:21763278). In patients with heart failure, processing and degradation of natriuretic peptides B occurs but is delayed, possibly due to a decrease in enzyme level or activity of CORIN and DPP4 (PubMed:25339504). {ECO:0000269|PubMed:10880574, ECO:0000269|PubMed:20489134, ECO:0000269|PubMed:21314817, ECO:0000269|PubMed:21482747, ECO:0000269|PubMed:21763278, ECO:0000269|PubMed:25339504}.; PTM: [Brain natriuretic peptide 32]: Undergoes further proteolytic cleavage by various proteases such as DPP4, MME and possibly FAP, to give rise to a variety of shorter peptides (PubMed:16254193, PubMed:19808300, PubMed:21314817, PubMed:21098034). Cleaved at Pro-104 by the prolyl endopeptidase FAP (seprase) activity (in vitro) (PubMed:21314817). Degraded by IDE (PubMed:21098034). During IDE degradation, the resulting products initially increase the activation of NPR1 and can also stimulate NPR2 to produce cGMP before the fragments are completely degraded and inactivated by IDE (in vitro) (PubMed:21098034). {ECO:0000269|PubMed:16254193, ECO:0000269|PubMed:19808300, ECO:0000269|PubMed:21098034, ECO:0000269|PubMed:21314817}.; PTM: O-glycosylated on at least seven residues (PubMed:20489134, PubMed:21763278, PubMed:16750161, PubMed:17349887, PubMed:21482747). In cardiomyocytes, glycosylation at Thr-97 is essential for the stability and processing of the extracellular natriuretic peptides B (PubMed:21482747). Glycosylation, especially at Thr-97, may also be important for brain natriuretic peptide 32 stability and/or extracellular distribution (PubMed:21763278). Glycosylation at Thr-97 appears to inhibit FURIN- or CORIN-mediated proteolytic processing, at least in HEK293 cells (PubMed:20489134, PubMed:21763278). {ECO:0000269|PubMed:16750161, ECO:0000269|PubMed:17349887, ECO:0000269|PubMed:20489134, ECO:0000269|PubMed:21482747, ECO:0000269|PubMed:21763278}.
Signal Peptide SIGNAL 1..26; /evidence=ECO:0000269|PubMed:2138890
Structure 3D X-ray crystallography (2)
Cross Reference PDB 1YK1; 3N56;
Mapped Pubmed ID 10636255; 11410403; 11750283; 11999635; 12015190; 12084525; 12601551; 12612980; 12742987; 12771003; 12832317; 12861161; 12890912; 14645255; 14726474; 14967157; 15118286; 15277419; 15525883; 15604421; 15616804; 15619076; 15644628; 15686715; 15732251; 15735222; 15875778; 15911064; 15947264; 16037399; 16061439; 16117728; 16179421; 16185779; 16189514; 16203929; 16236896; 16236924; 16236931; 16298451; 16338248; 16338261; 16338262; 16338263; 16338268; 16377932; 16386619; 16446217; 16495466; 16546444; 16594987; 16624649; 16644347; 16648193; 16697117; 16716660; 16722030; 16733597; 16733598; 16754798; 16801175; 16829184; 16831981; 16875975; 16937127; 16940194; 16962475; 16962477; 17086116; 17097992; 17099013; 17112494; 17149558; 17175893; 17186137; 17323015; 17340039; 17343213; 17365940; 17381357; 17412758; 17478552; 17482153; 17490778; 17517347; 17519779; 17554401; 17567649; 17607499; 17607502; 17643631; 17662495; 17669797; 17690842; 17719005; 17721754; 17785934; 17822384; 17879024; 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33058960; 33121714; 33128247; 33133305; 33160126; 33221779; 33245872; 33248864; 33270715; 33279592; 33353469; 33375031; 33455978; 33510196; 33563897; 33678076; 33691659; 33720941; 33888145; 33955184; 34044561; 34044565; 34087618; 34143704; 34286378; 34415953; 34556318; 34763639; 34798808; 34980326;
Motif
Gene Encoded By
Mass 14,726
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda