General Information of Drug Off-Target (DOT) (ID: OTMQNTNX)

DOT Name Natriuretic peptides A (NPPA)
Synonyms Atrial natriuretic factor prohormone; proANF; Atrial natriuretic peptide prohormone; preproANP; proANP; Atriopeptigen; Cardiodilatin; CDD; preproCDD-ANF
Gene Name NPPA
Related Disease
Lung cancer ( )
Stroke ( )
Adenocarcinoma ( )
Alzheimer disease ( )
Atherosclerosis ( )
Atrial fibrillation ( )
Breast cancer ( )
Cardiac failure ( )
Congestive heart failure ( )
Coronary heart disease ( )
Coronary ischemia ( )
Diabetic kidney disease ( )
Dilated cardiomyopathy 1A ( )
Essential hypertension ( )
Familial hypertrophic cardiomyopathy ( )
Hypertrophic cardiomyopathy ( )
Hypotension ( )
Liver cirrhosis ( )
Lung neoplasm ( )
Myocardial infarction ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Patent ductus arteriosus ( )
Prostate cancer ( )
Prostate neoplasm ( )
Pulmonary hypertension ( )
Atrial fibrillation, familial, 6 ( )
Cardiovascular disease ( )
Melanoma ( )
Skin cancer ( )
Skin neoplasm ( )
Atrial standstill ( )
Familial atrial fibrillation ( )
Acute kidney injury ( )
Rheumatoid arthritis ( )
Atrial standstill 2 ( )
Cardiomyopathy ( )
Glaucoma/ocular hypertension ( )
Myocardial ischemia ( )
Psoriasis ( )
Type-1/2 diabetes ( )
Dilated cardiomyopathy ( )
UniProt ID
ANF_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1ANP; 1YK0; 3N57; 7BRH; 7BRJ; 7BRK
Pfam ID
PF00212
Sequence
MSSFSTTTVSFLLLLAFQLLGQTRANPMYNAVSNADLMDFKNLLDHLEEKMPLEDEVVPP
QVLSEPNEEAGAALSPLPEVPPWTGEVSPAQRDGGALGRGPWDSSDRSALLKSKLRALLT
APRSLRRSSCFGGRMDRIGAQSGLGCNSFRY
Function
[Atrial natriuretic peptide]: Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism. Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses. Regulates vasodilation, natriuresis, diuresis and aldosterone synthesis and is therefore essential for regulating blood pressure, controlling the extracellular fluid volume and maintaining the fluid-electrolyte balance. Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts. Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension. In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis. This includes up-regulating lipid metabolism and mitochondrial oxygen utilization by activating the AMP-activated protein kinase (AMPK), and increasing energy expenditure by acting via MAPK11 to promote the UCP1-dependent thermogenesis of brown adipose tissue. Binds the clearance receptor NPR3 which removes the hormone from circulation ; [Long-acting natriuretic peptide]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report, in vivo it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by atrial natriuretic peptide and vessel dilator. Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption ; [Vessel dilator]: May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides. Possibly functions in protein excretion in urine by maintaining the integrity of the proximal tubules and enhancing protein excretion by decreasing proximal tubular protein reabsorption ; [Kaliuretic peptide]: May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. May have a role in potassium excretion but not sodium excretion (natriuresis). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption ; [Urodilatin]: Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis. Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance. Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1. Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney ; [Auriculin-D]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips; [Auriculin-B]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips; [Auriculin-A]: May have a role in cardio-renal homeostasis through regulation of regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, vasodilates intestinal smooth muscle but not smooth muscle strips; [Atriopeptin-2]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal and vascular smooth muscle strips; [Atriopeptin-1]: May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal smooth muscle but not vascular smooth muscle strips.
Tissue Specificity
.Detected in the kidney distal tubular cells (at protein level) . Present in urine (at protein level) .; [Atrial natriuretic peptide]: Detected in atrial and ventricular plasma samples, and in adipocytes (at protein level) . Detected in urine in one study . However, was not detected in urine in another study . In the brain, predominantly expressed in the gray matter with very weak expression in the white matter (at protein level) . Localizes to astrocyte-like structures throughout the white matter, and in the cerebral vessels detected in the leptomeningeal and parenchymal vessels, and endothelium and smooth muscle layers (at protein level) . Relatively low levels of expression in the kidneys compared to urodilatin (at protein level) .
KEGG Pathway
cGMP-PKG sig.ling pathway (hsa04022 )
cAMP sig.ling pathway (hsa04024 )
HIF-1 sig.ling pathway (hsa04066 )
Vascular smooth muscle contraction (hsa04270 )
Thermogenesis (hsa04714 )
Oxytocin sig.ling pathway (hsa04921 )
Regulation of lipolysis in adipocytes (hsa04923 )
Renin secretion (hsa04924 )
Aldosterone synthesis and secretion (hsa04925 )
African trypanosomiasis (hsa05143 )
Reactome Pathway
Physiological factors (R-HSA-5578768 )
Amyloid fiber formation (R-HSA-977225 )
YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung cancer DISCM4YA Definitive Genetic Variation [1]
Stroke DISX6UHX Definitive Biomarker [2]
Adenocarcinoma DIS3IHTY Strong Therapeutic [3]
Alzheimer disease DISF8S70 Strong Biomarker [4]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Atrial fibrillation DIS15W6U Strong Biomarker [6]
Breast cancer DIS7DPX1 Strong Altered Expression [7]
Cardiac failure DISDC067 Strong Biomarker [8]
Congestive heart failure DIS32MEA Strong Biomarker [8]
Coronary heart disease DIS5OIP1 Strong Genetic Variation [9]
Coronary ischemia DISDJJ5G Strong Biomarker [10]
Diabetic kidney disease DISJMWEY Strong Genetic Variation [11]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [12]
Essential hypertension DIS7WI98 Strong Genetic Variation [13]
Familial hypertrophic cardiomyopathy DISQ89HN Strong Biomarker [14]
Hypertrophic cardiomyopathy DISQG2AI Strong Altered Expression [15]
Hypotension DISYNSM9 Strong Biomarker [16]
Liver cirrhosis DIS4G1GX Strong Biomarker [17]
Lung neoplasm DISVARNB Strong Therapeutic [18]
Myocardial infarction DIS655KI Strong Altered Expression [19]
Neoplasm DISZKGEW Strong Altered Expression [20]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [21]
Obesity DIS47Y1K Strong Genetic Variation [22]
Patent ductus arteriosus DIS9P8YS Strong Biomarker [23]
Prostate cancer DISF190Y Strong Therapeutic [3]
Prostate neoplasm DISHDKGQ Strong Therapeutic [3]
Pulmonary hypertension DIS1RSP5 Strong Biomarker [24]
Atrial fibrillation, familial, 6 DISZBKHJ Moderate Autosomal dominant [25]
Cardiovascular disease DIS2IQDX moderate Biomarker [26]
Melanoma DIS1RRCY moderate Therapeutic [27]
Skin cancer DISTM18U moderate Therapeutic [27]
Skin neoplasm DIS16DDV moderate Therapeutic [27]
Atrial standstill DISFHGZA Supportive Autosomal dominant [28]
Familial atrial fibrillation DISL4AGF Supportive Autosomal dominant [29]
Acute kidney injury DISXZG0T Disputed Biomarker [30]
Rheumatoid arthritis DISTSB4J Disputed Biomarker [31]
Atrial standstill 2 DISWNITN Limited Autosomal recessive [28]
Cardiomyopathy DISUPZRG Limited Altered Expression [32]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [33]
Myocardial ischemia DISFTVXF Limited Genetic Variation [34]
Psoriasis DIS59VMN Limited Genetic Variation [35]
Type-1/2 diabetes DISIUHAP Limited Biomarker [36]
Dilated cardiomyopathy DISX608J No Known Autosomal recessive [37]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Aldosterone DM9S2JW Approved Natriuretic peptides A (NPPA) decreases the secretion of Aldosterone. [70]
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This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Amlodipine DMBDAZV Approved Natriuretic peptides A (NPPA) increases the Cardiovascular disorder ADR of Amlodipine. [71]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Natriuretic peptides A (NPPA). [38]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Natriuretic peptides A (NPPA). [64]
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28 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Natriuretic peptides A (NPPA). [39]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Natriuretic peptides A (NPPA). [40]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Natriuretic peptides A (NPPA). [41]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Natriuretic peptides A (NPPA). [42]
Progesterone DMUY35B Approved Progesterone increases the expression of Natriuretic peptides A (NPPA). [43]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Natriuretic peptides A (NPPA). [23]
Cocaine DMSOX7I Approved Cocaine increases the expression of Natriuretic peptides A (NPPA). [45]
Hydrocortisone DMGEMB7 Approved Hydrocortisone increases the expression of Natriuretic peptides A (NPPA). [46]
Isoproterenol DMK7MEY Approved Isoproterenol increases the expression of Natriuretic peptides A (NPPA). [47]
Carvedilol DMHTEAO Approved Carvedilol decreases the expression of Natriuretic peptides A (NPPA). [49]
Epirubicin DMPDW6T Approved Epirubicin increases the expression of Natriuretic peptides A (NPPA). [50]
Atenolol DMNKG1Z Approved Atenolol decreases the expression of Natriuretic peptides A (NPPA). [51]
Spironolactone DM2AQ5N Approved Spironolactone decreases the expression of Natriuretic peptides A (NPPA). [52]
Furosemide DMMQ8ZG Approved Furosemide decreases the expression of Natriuretic peptides A (NPPA). [53]
Felodipine DMOSW35 Approved Felodipine affects the expression of Natriuretic peptides A (NPPA). [54]
Enalapril DMNFUZR Approved Enalapril decreases the expression of Natriuretic peptides A (NPPA). [55]
Naloxone DM3FXMA Approved Naloxone decreases the expression of Natriuretic peptides A (NPPA). [56]
Labetalol DMK8U72 Approved Labetalol decreases the activity of Natriuretic peptides A (NPPA). [57]
Mannitol DMSCDY9 Approved Mannitol increases the expression of Natriuretic peptides A (NPPA). [58]
Alprostadil DMWH7NQ Approved Alprostadil decreases the expression of Natriuretic peptides A (NPPA). [59]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Natriuretic peptides A (NPPA). [61]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Natriuretic peptides A (NPPA). [62]
Verapamil DMA7PEW Phase 2/3 Trial Verapamil increases the expression of Natriuretic peptides A (NPPA). [63]
Omapatrilat DMAGUY0 Terminated Omapatrilat increases the expression of Natriuretic peptides A (NPPA). [65]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Natriuretic peptides A (NPPA). [66]
Manganese DMKT129 Investigative Manganese decreases the expression of Natriuretic peptides A (NPPA). [67]
Irbesartan DMTP1DC Investigative Irbesartan increases the expression of Natriuretic peptides A (NPPA). [68]
Lisinopril DMUOK4C Investigative Lisinopril decreases the expression of Natriuretic peptides A (NPPA). [69]
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⏷ Show the Full List of 28 Drug(s)
2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Phenylephrine DMZHUO5 Approved Phenylephrine increases the secretion of Natriuretic peptides A (NPPA). [48]
Cilazapril DM4V6JA Approved Cilazapril affects the secretion of Natriuretic peptides A (NPPA). [60]
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References

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