NPPB
This gene is a member of the natriuretic peptide family and encodes a secreted protein which functions as a cardiac hormone. The protein undergoes two cleavage events, one within the cell and a second after secretion into the blood. The protein's biological actions include natriuresis, diuresis, vasorelaxation, inhibition of renin and aldosterone secretion, and a key role in cardiovascular homeostasis. A high concentration of this protein in the bloodstream is indicative of heart failure. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Mutations in this gene have been associated with postmenopausal osteoporosis. [provided by RefSeq, Nov 2014]
Full Name
Natriuretic Peptide B
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).
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).
BNP(3-32)
May have a role in cardio-renal homeostasis (PubMed:17372040).
Able to promote the production of cGMP (PubMed:17372040).
Biological Process
Antimicrobial humoral immune response mediated by antimicrobial peptideIDA:UniProtKB
Blood vessel diameter maintenance1 PublicationNAS:UniProtKB
Body fluid secretionManual Assertion Based On ExperimentTAS:UniProtKB
Cardiac conduction system development1 PublicationNAS:BHF-UCL
Cell surface receptor signaling pathway1 PublicationNAS:UniProtKB
cGMP biosynthetic processManual Assertion Based On ExperimentIDA:GO_Central
cGMP-mediated signalingManual Assertion Based On ExperimentIBA:GO_Central
Killing of cells of another organismIDA:UniProtKB
Negative regulation of angiogenesisManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of cell growth1 PublicationNAS:UniProtKB
Negative regulation of systemic arterial blood pressureManual Assertion Based On ExperimentIBA:GO_Central
Neuropeptide signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of renal sodium excretionManual Assertion Based On ExperimentTAS:UniProtKB
Positive regulation of urine volumeManual Assertion Based On ExperimentTAS:UniProtKB
Protein foldingManual Assertion Based On ExperimentIDA:CAFA
Receptor guanylyl cyclase signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of blood pressure1 PublicationNAS:UniProtKB
Regulation of vascular permeabilityManual Assertion Based On ExperimentTAS:UniProtKB
VasodilationIEA:UniProtKB-KW
Cellular Location
NT-proBNP
Secreted
Detected in blood.
proBNP(3-108)
Secreted
Detected in blood.
Brain natriuretic peptide 32
Secreted
Detected in blood.
BNP(3-32)
Secreted
Detected in blood.
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).
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).
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).
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