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Nppa

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 (PubMed:15741263, PubMed:16875975, PubMed:18835931, PubMed:21672517, PubMed:22307324, PubMed:2532366, PubMed:2825692, PubMed:7595132, PubMed:7720651, PubMed:8087923, PubMed:8653797). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses (PubMed:1660465, PubMed:1672777, PubMed:21098034, PubMed:2162527, PubMed:22307324, PubMed:25401746, PubMed:2825692, PubMed:7720651, PubMed:8384600, PubMed:9893117). 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 (PubMed:2532366, PubMed:2825692, PubMed:7595132, PubMed:7720651, PubMed:8087923, PubMed:8653797). Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (PubMed:16875975). Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension (By similarity). In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis (PubMed:15741263, PubMed:18835931, PubMed:21672517, PubMed:22307324). 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 (PubMed:15741263, PubMed:18835931, PubMed:21672517, PubMed:22307324). Binds the clearance receptor NPR3 which removes the hormone from circulation (PubMed:1672777).

Long-acting natriuretic peptide

May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis (PubMed:2532366, PubMed:2825692, PubMed:7595132, PubMed:7955907, PubMed:8087923, PubMed:8653797). In vitro, promotes the production of cGMP and induces vasodilation (PubMed:2825692). May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (PubMed:7720651). 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 (By similarity). Appears to bind to specific receptors that are distinct from the receptors bound by atrial natriuretic peptide and vessel dilator (PubMed:2162527, PubMed:2825692). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (PubMed:11145122).

Vessel dilator

May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation (PubMed:2532366, PubMed:7595132, PubMed:7955907, PubMed:8087923, PubMed:8653797). In vitro, promotes the production of cGMP and induces vasodilation (PubMed:2825692). May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (PubMed:7595132, PubMed:7720651). 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 (PubMed:7831500). Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides (PubMed:2162527, PubMed:2825692). 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 (PubMed:11145122).

Kaliuretic peptide

May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis (PubMed:2825692, PubMed:7595132, PubMed:8087923). In vitro, promotes the production of cGMP and induces vasodilation (PubMed:2825692). May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (PubMed:7595132, PubMed:7720651). May have a role in potassium excretion but not sodium excretion (natriuresis) (PubMed:8087923). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (PubMed:11145122).

Urodilatin

Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis (PubMed:8351194, PubMed:8779891, PubMed:8853410). Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance (PubMed:2528951, PubMed:8351194, PubMed:8779891, PubMed:8853410). Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1 (PubMed:8384600, PubMed:9893117). Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney (PubMed:8384600, PubMed:8779891).

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.

Involvement in disease

Atrial standstill 2

ATRST2

A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm.

None

The disease is caused by variants affecting the gene represented in this entry.

Atrial fibrillation, familial, 6

ATFB6

A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

The precursor molecule is proteolytically cleaved by CORIN at Arg-123 to produce atrial natriuretic peptide (PubMed:10880574, PubMed:14559895, PubMed:7984506). Undergoes further proteolytic cleavage by unknown proteases to give rise to long-acting natriuretic peptide, vessel dilator and kaliuretic peptide (PubMed:2532366, PubMed:7955907, PubMed:7984506). Additional processing gives rise to the auriculin and atriopeptin peptides (By similarity). In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin (PubMed:2972874, PubMed:8351194, PubMed:9794555).

Atrial natriuretic peptide

Cleavage by MME initiates degradation of the factor and thereby regulates its activity (PubMed:16254193, PubMed:2972276). Degraded by IDE (in vitro) (PubMed:21098034). During IDE degradation, the resulting products can temporarily stimulate NPR2 to produce cGMP, before the fragments are completely degraded and inactivated by IDE (in vitro) (PubMed:21098034).

Urodilatin

Degraded by IDE.

Urodilatin

Phosphorylation on Ser-129 decreases vasorelaxant activity.

Sequence similarities

Belongs to the natriuretic peptide family.

Tissue specificity

Urodilatin

Detected in the kidney distal tubular cells (at protein level) (PubMed:8384600, PubMed:9794555). Present in urine (at protein level) (PubMed:2972874, PubMed:8351194, PubMed:8779891, PubMed:9794555).

Atrial natriuretic peptide

Detected in atrial and ventricular plasma samples, and in adipocytes (at protein level) (PubMed:21672517, PubMed:22291141). Detected in urine in one study (PubMed:8351194). However, was not detected in urine in another study (PubMed:7984506). In the brain, predominantly expressed in the gray matter with very weak expression in the white matter (at protein level) (PubMed:30534047). 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) (PubMed:30534047). Relatively low levels of expression in the kidneys compared to urodilatin (at protein level) (PubMed:8384600, PubMed:9794555).

Cellular localization

  • Long-acting natriuretic peptide
  • Secreted
  • Detected in blood.
  • Vessel dilator
  • Secreted
  • Detected in blood.
  • Kaliuretic peptide
  • Secreted
  • Detected in blood.
  • Urodilatin
  • Secreted
  • Detected in urine (PubMed:2972874, PubMed:8351194, PubMed:8779891, PubMed:9794555). Not detected in blood (PubMed:8351194). Increased electrolytes, osmolality and intracellular cAMP levels increase peptide secretion/excretion (PubMed:8351194, PubMed:8779891, PubMed:8853410, PubMed:9893117).
  • Atrial natriuretic peptide
  • Secreted
  • Perikaryon
  • Cell projection
  • Detected in blood (PubMed:15741263, PubMed:18835931, PubMed:2532366, PubMed:7955907, PubMed:7984506, PubMed:8351194, PubMed:8653797, PubMed:8779891). Detected in urine in one study (PubMed:8351194). However, in another study, was not detected in urine (PubMed:7984506). Detected in cytoplasmic bodies and neuronal processes of pyramidal neurons (layers II-VI) (PubMed:30534047). Increased secretion in response to the vasopressin AVP (By similarity). Likely to be secreted in response to an increase in atrial pressure or atrial stretch (PubMed:2532366). In kidney cells, secretion increases in response to activated guanylyl cyclases and increased intracellular cAMP levels (PubMed:9893117). Plasma levels increase 15 minutes after a high-salt meal, and decrease back to normal plasma levels 1 hr later (PubMed:8779891).
  • Atriopeptin-3
  • Secreted
  • Detected in blood. Slight increase in secretion in response to the vasopressin AVP.

Alternative names

  • ANP
  • PND
  • ANP
  • PND
  • NPPA
  • Natriuretic peptides A
  • Atrial natriuretic factor prohormone
  • Atrial natriuretic peptide prohormone
  • Atriopeptigen
  • Cardiodilatin
  • preproCDD-ANF
  • proANF
  • preproANP
  • proANP
  • CDD

Target type

Proteins

Molecular weight

16396Da

We found 28 products in 3 categories

Assay Kits

Target

Reactive species

Detection method

Proteins & Peptides

Target

Species of origin