P01161 · ANF_RAT
- ProteinNatriuretic peptides A
- GeneNppa
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids152 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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 (By similarity).
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:15117952).
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:7831500).
Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (By similarity).
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 (By similarity).
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 (By similarity).
Binds the clearance receptor NPR3 which removes the hormone from circulation (By similarity).
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:15117952).
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:7831500).
Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (By similarity).
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 (By similarity).
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 (By similarity).
Binds the clearance receptor NPR3 which removes the hormone from circulation (By similarity).
Long-acting natriuretic peptide
May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis (By similarity).
In vitro, promotes the production of cGMP and induces vasodilation (By similarity).
May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity).
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 (PubMed:7831500).
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 (By similarity).
In vitro, promotes the production of cGMP and induces vasodilation (By similarity).
May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity).
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 (PubMed:7831500).
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 (By similarity).
Vessel dilator
May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation (By similarity).
In vitro, promotes the production of cGMP and induces vasodilation (By similarity).
May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity).
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 (PubMed:7831500).
Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides (By similarity).
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 (By similarity).
In vitro, promotes the production of cGMP and induces vasodilation (By similarity).
May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity).
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 (PubMed:7831500).
Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides (By similarity).
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 (By similarity).
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.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 122-123 | Cleavage; by CORIN | ||||
Sequence: RS | ||||||
Site | 129-130 | Cleavage; by MME | ||||
Sequence: CF |
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNatriuretic peptides A
- Alternative names
- Cleaved into 12 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP01161
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Long-acting natriuretic peptide
Note: Detected in blood.
Vessel dilator
Note: Detected in blood.
Kaliuretic peptide
Note: Detected in blood.
Urodilatin
Note: Detected in urine. Not detected in blood. Increased electrolytes, osmolality and intracellular cAMP levels increase peptide secretion/excretion.
Atrial natriuretic peptide
Note: Detected in blood (PubMed:2966345, PubMed:3160114).
Detected in urine in one study (By similarity).
However, in another study, was not detected in urine (By similarity).
Detected in cytoplasmic bodies and neuronal processes of pyramidal neurons (layers II-VI) (By similarity).
Increased secretion in response to the vasopressin AVP (PubMed:3160114).
Also likely to be secreted in response to an increase in atrial pressure or atrial stretch (By similarity).
In kidney cells, secretion increases in response to activated guanylyl cyclases and increased intracellular cAMP levels (By similarity).
Plasma levels increase 15 minutes after a high-salt meal, and decrease back to normal plasma levels 1 hr later (By similarity).
Detected in urine in one study (By similarity).
However, in another study, was not detected in urine (By similarity).
Detected in cytoplasmic bodies and neuronal processes of pyramidal neurons (layers II-VI) (By similarity).
Increased secretion in response to the vasopressin AVP (PubMed:3160114).
Also likely to be secreted in response to an increase in atrial pressure or atrial stretch (By similarity).
In kidney cells, secretion increases in response to activated guanylyl cyclases and increased intracellular cAMP levels (By similarity).
Plasma levels increase 15 minutes after a high-salt meal, and decrease back to normal plasma levels 1 hr later (By similarity).
Atriopeptin-3
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, peptide, propeptide, chain, modified residue, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MGSFSITKGFFLFLAFWLPGHIGA | ||||||
Peptide | PRO_0000449771 | 25-54 | Long-acting natriuretic peptide | |||
Sequence: NPVYSAVSNTDLMDFKNLLDHLEEKMPVED | ||||||
Propeptide | PRO_0000001505 | 25-122 | ||||
Sequence: NPVYSAVSNTDLMDFKNLLDHLEEKMPVEDEVMPPQALSEQTDEAGAALSSLSEVPPWTGEVNPSQRDGGALGRGPWDPSDRSALLKSKLRALLAGPR | ||||||
Chain | PRO_0000449770 | 25-150 | Natriuretic peptides A | |||
Sequence: NPVYSAVSNTDLMDFKNLLDHLEEKMPVEDEVMPPQALSEQTDEAGAALSSLSEVPPWTGEVNPSQRDGGALGRGPWDPSDRSALLKSKLRALLAGPRSLRRSSCFGGRIDRIGAQSGLGCNSFRY | ||||||
Peptide | PRO_0000449772 | 55-91 | Vessel dilator | |||
Sequence: EVMPPQALSEQTDEAGAALSSLSEVPPWTGEVNPSQR | ||||||
Propeptide | PRO_0000449773 | 92-102 | ||||
Sequence: DGGALGRGPWD | ||||||
Peptide | PRO_0000449774 | 103-122 | Kaliuretic peptide | |||
Sequence: PSDRSALLKSKLRALLAGPR | ||||||
Peptide | PRO_0000449776 | 118-150 | Auriculin-C | |||
Sequence: LAGPRSLRRSSCFGGRIDRIGAQSGLGCNSFRY | ||||||
Peptide | PRO_0000449775 | 119-150 | Urodilatin | |||
Sequence: AGPRSLRRSSCFGGRIDRIGAQSGLGCNSFRY | ||||||
Peptide | PRO_0000449777 | 120-144 | Auriculin-D | |||
Sequence: GPRSLRRSSCFGGRIDRIGAQSGLG | ||||||
Peptide | PRO_0000391785 | 123-150 | Atrial natriuretic peptide | |||
Sequence: SLRRSSCFGGRIDRIGAQSGLGCNSFRY | ||||||
Peptide | PRO_0000001507 | 126-149 | Auriculin-A | |||
Sequence: RSSCFGGRIDRIGAQSGLGCNSFR | ||||||
Peptide | PRO_0000001506 | 126-150 | Auriculin-B | |||
Sequence: RSSCFGGRIDRIGAQSGLGCNSFRY | ||||||
Peptide | PRO_0000001510 | 127-147 | Atriopeptin-1 | |||
Sequence: SSCFGGRIDRIGAQSGLGCNS | ||||||
Peptide | PRO_0000001509 | 127-149 | Atriopeptin-2 | |||
Sequence: SSCFGGRIDRIGAQSGLGCNSFR | ||||||
Peptide | PRO_0000001508 | 127-150 | Atriopeptin-3 | |||
Sequence: SSCFGGRIDRIGAQSGLGCNSFRY | ||||||
Modified residue | 128 | Phosphoserine | ||||
Sequence: S | ||||||
Disulfide bond | 129↔145 | |||||
Sequence: CFGGRIDRIGAQSGLGC |
Post-translational modification
The precursor molecule is proteolytically cleaved by CORIN at Arg-122 to produce the atrial natriuretic peptide. Undergoes further proteolytic cleavage by unknown proteases to give rise to long-acting natriuretic peptide, vessel dilator and kaliuretic peptide (By similarity).
Additional processing gives rise to the auriculin and atriopeptin peptides (PubMed:3160114, PubMed:6232612, PubMed:6233494, PubMed:6419347).
In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin (By similarity).
Additional processing gives rise to the auriculin and atriopeptin peptides (PubMed:3160114, PubMed:6232612, PubMed:6233494, PubMed:6419347).
In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin (By similarity).
Atrial natriuretic peptide
Cleavage by MME initiates degradation of the factor and thereby regulates its activity (PubMed:2966343).
Degradation by IDE results in reduced activation of NPR1 (in vitro) (By similarity).
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) (By similarity).
Degradation by IDE results in reduced activation of NPR1 (in vitro) (By similarity).
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) (By similarity).
Urodilatin
Degraded by IDE.
Urodilatin
Phosphorylation on Ser-128 decreases vasorelaxant activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
High levels of expression in the atria compared to the ventricles (PubMed:1837590).
Very low levels of expression detected in extracardiac tissues such as the brain, hypothalamus, pituitary, lung and aorta (PubMed:1837590).
Very low levels of expression detected in extracardiac tissues such as the brain, hypothalamus, pituitary, lung and aorta (PubMed:1837590).
Auriculin-A
Atria (at protein level).
Auriculin-B
Atria (at protein level).
Auriculin-C
Atria (at protein level).
Auriculin-D
Atria (at protein level).
Atrial natriuretic peptide
High levels of expression in the atria with very low levels of expression in the ventricles (at protein level) (PubMed:2525379).
Relatively low levels of expression detected in the brain compared to the atria (at protein level) (PubMed:2525379).
Relatively low levels of expression detected in the brain compared to the atria (at protein level) (PubMed:2525379).
Atriopeptin-1
Atria (at protein level).
Atriopeptin-2
Atria (at protein level).
Gene expression databases
Interaction
Subunit
Atrial natriuretic peptide
Homodimer; disulfide-linked antiparallel dimer.
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 54-104 | Disordered | ||||
Sequence: DEVMPPQALSEQTDEAGAALSSLSEVPPWTGEVNPSQRDGGALGRGPWDPS | ||||||
Region | 146-150 | Important for degradation of atrial natriuretic peptide by IDE | ||||
Sequence: NSFRY |
Sequence similarities
Belongs to the natriuretic peptide family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length152
- Mass (Da)16,556
- Last updated1986-07-21 v1
- ChecksumD8AAB2191E29519F
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I5Y501 | A0A8I5Y501_RAT | Nppa | 199 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M15868 EMBL· GenBank· DDBJ | AAA40736.1 EMBL· GenBank· DDBJ | mRNA | ||
X00665 EMBL· GenBank· DDBJ | CAA25285.1 EMBL· GenBank· DDBJ | mRNA | ||
K02062 EMBL· GenBank· DDBJ | AAA40735.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X01118 EMBL· GenBank· DDBJ | CAA25586.1 EMBL· GenBank· DDBJ | mRNA | ||
M27498 EMBL· GenBank· DDBJ | AAA40737.1 EMBL· GenBank· DDBJ | mRNA |