UniProtKB - P05125 (ANF_MOUSE)
Natriuretic peptides A
Nppa
Functioni
Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism (PubMed:8760210, PubMed:22437503, PubMed:12890708).
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:12890708).
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:8760210, PubMed:22437503).
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 (PubMed:22437503).
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).
By similarity3 PublicationsMay 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 (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 (By similarity).
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).
By similarityMay 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.
By similarityMay 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.
By similarityHormone 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.
By similarityMay have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips.
By similarityMay have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips.
By similarityMay 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.
By similarityMay 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.
By similarityMay 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.
By similarityCaution
GO - Molecular functioni
- hormone activity Source: MGI
- hormone receptor binding Source: MGI
- neuropeptide hormone activity Source: MGI
- neuropeptide receptor binding Source: MGI
- signaling receptor binding Source: MGI
GO - Biological processi
- cardiac muscle hypertrophy in response to stress Source: MGI
- cGMP biosynthetic process Source: UniProtKB
- cGMP-mediated signaling Source: MGI
- female pregnancy Source: UniProtKB
- negative regulation of blood pressure Source: MGI
- negative regulation of canonical Wnt signaling pathway Source: MGI
- negative regulation of cell growth Source: MGI
- negative regulation of collecting lymphatic vessel constriction Source: MGI
- negative regulation of epidermal growth factor receptor signaling pathway Source: MGI
- negative regulation of JUN kinase activity Source: MGI
- negative regulation of systemic arterial blood pressure Source: MGI
- neuropeptide signaling pathway Source: MGI
- positive regulation of cardiac muscle contraction Source: MGI
- positive regulation of cGMP-mediated signaling Source: MGI
- positive regulation of delayed rectifier potassium channel activity Source: MGI
- positive regulation of heart rate Source: MGI
- positive regulation of histamine secretion by mast cell Source: MGI
- positive regulation of potassium ion export across plasma membrane Source: MGI
- protein folding Source: MGI
- receptor guanylyl cyclase signaling pathway Source: UniProtKB
- regulation of atrial cardiac muscle cell membrane repolarization Source: MGI
- regulation of blood pressure Source: UniProtKB
- regulation of calcium ion transmembrane transport via high voltage-gated calcium channel Source: MGI
- regulation of high voltage-gated calcium channel activity Source: MGI
- sodium ion export across plasma membrane Source: MGI
- vasodilation Source: UniProtKB-KW
Keywordsi
Molecular function | Hormone, Vasoactive, Vasodilator |
Enzyme and pathway databases
Reactomei | R-MMU-5578768, Physiological factors |
Names & Taxonomyi
Protein namesi | Recommended name: Natriuretic peptides A1 PublicationAlternative name(s): Atrial natriuretic factor prohormoneBy similarity Short name: preproANFBy similarity Short name: proANF1 Publication Atrial natriuretic peptide prohormoneBy similarity Short name: preproANPBy similarity Short name: proANP1 Publication AtriopeptigenBy similarity CardiodilatinBy similarity Short name: CDDBy similarity preproCDD-ANFBy similarity Cleaved into the following 12 chains: Alternative name(s): Long-acting natriuretic hormoneCurated Short name: LANHCurated Pro atrial natriuretic factor 1-30By similarity Short name: proANF 1-30By similarity Pro atrial natriuretic peptide 1-30Curated Short name: proANP 1-30Curated Alternative name(s): Pro atrial natriuretic factor 31-67By similarity Short name: proANF 31-67By similarity Pro atrial natriuretic peptide 31-67Curated Short name: proANP 31-67Curated Alternative name(s): Pro atrial natriuretic factor 79-98By similarity Short name: proANF 79-98By similarity Pro atrial natriuretic peptide 79-98Curated Short name: proANP 79-98Curated Alternative name(s): CDD 95-126By similarity CDD-ANP (95-126)By similarity Pro atrial natriuretic peptide 95-126By similarity Short name: proANP 95-126By similarity Auriculin-CCurated Alternative name(s): Atrial natriuretic factor 1-33By similarity Short name: ANF 1-33By similarity Auriculin-DCurated Alternative name(s): Atrial natriuretic factor 3-33By similarity Short name: ANF 3-33By similarity Alternative name(s): Alpha-atrial natriuretic peptideBy similarity Alpha-hANPBy similarity Atrial natriuretic factor1 Publication Short name: ANF1 Publication CDD-ANFBy similarity CDD-ANP (99-126)By similarity CardionatrinBy similarity Pro atrial natriuretic factor 99-126By similarity Short name: proANF 99-126By similarity Auriculin-BCurated Alternative name(s): Atrial natriuretic factor 8-33By similarity Short name: ANF 8-33By similarity Auriculin-ABy similarity Atriopeptin-1By similarity Alternative name(s): Atriopeptin IBy similarity Atriopeptin-2By similarity Alternative name(s): Atriopeptin IIBy similarity Atriopeptin-3By similarity Alternative name(s): Atriopeptin IIIBy similarity |
Gene namesi | Name:Nppa Synonyms:Pnd |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:97367, Nppa |
VEuPathDBi | HostDB:ENSMUSG00000041616 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Note: Detected in blood.By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Detected in blood.By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Detected in blood.By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Detected in urine. Not detected in blood. Increased electrolytes, osmolality and intracellular cAMP levels increase peptide secretion/excretion.By similarity
Extracellular region or secreted
- Secreted By similarity
Other locations
- Perikaryon By similarity
- Cell projection By similarity
Note: Detected in blood. Detected in urine in one study. However, in another study, was not detected in urine. Detected in cytoplasmic bodies and neuronal processes of pyramidal neurons (layers II-VI) (By similarity). 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. In kidney cells, secretion increases in response to activated guanylyl cyclases and increased intracellular cAMP levels. Plasma levels increase 15 minutes after a high-salt meal, and decrease back to normal plasma levels 1 hr later (By similarity).By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Detected in blood. Slight increase in secretion in response to the vasopressin AVP.By similarity
Extracellular region or secreted
- extracellular space Source: MGI
Lysosome
- mast cell granule Source: MGI
Nucleus
- nucleus Source: MGI
Other locations
- brush border Source: MGI
- cell projection Source: UniProtKB-SubCell
- cytoplasm Source: MGI
- perikaryon Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: MGI
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Cell projection, SecretedPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 122 | R → A: Abolishes maturation and cleavage by CORIN. 1 Publication | 1 | |
Mutagenesisi | 125 | R → A: Does not affect maturation and cleavage by CORIN. 1 Publication | 1 | |
Mutagenesisi | 126 | R → A: Does not affect maturation and cleavage by CORIN. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | By similarityAdd BLAST | 24 | |
ChainiPRO_0000449735 | 25 – 150 | Natriuretic peptides ABy similarityAdd BLAST | 126 | |
PropeptideiPRO_0000001495 | 25 – 122 | CuratedAdd BLAST | 98 | |
PeptideiPRO_0000449736 | 25 – 54 | Long-acting natriuretic peptideBy similarityAdd BLAST | 30 | |
PeptideiPRO_0000449737 | 55 – 91 | Vessel dilatorBy similarityAdd BLAST | 37 | |
PropeptideiPRO_0000449738 | 92 – 102 | By similarityAdd BLAST | 11 | |
PeptideiPRO_0000449739 | 103 – 122 | Kaliuretic peptideBy similarityAdd BLAST | 20 | |
PeptideiPRO_0000449740 | 118 – 150 | Auriculin-CBy similarityAdd BLAST | 33 | |
PeptideiPRO_0000449741 | 119 – 150 | UrodilatinBy similarityAdd BLAST | 32 | |
PeptideiPRO_0000449742 | 120 – 144 | Auriculin-DBy similarityAdd BLAST | 25 | |
PeptideiPRO_0000391784 | 123 – 150 | Atrial natriuretic peptide1 PublicationAdd BLAST | 28 | |
PeptideiPRO_0000001496 | 126 – 150 | Auriculin-BBy similarityAdd BLAST | 25 | |
PeptideiPRO_0000001497 | 126 – 149 | Auriculin-ABy similarityAdd BLAST | 24 | |
PeptideiPRO_0000449743 | 127 – 150 | Atriopeptin-3By similarityAdd BLAST | 24 | |
PeptideiPRO_0000001498 | 127 – 149 | Atriopeptin-1By similarityAdd BLAST | 23 | |
PeptideiPRO_0000001499 | 127 – 147 | Atriopeptin-2By similarityAdd BLAST | 21 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 128 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 129 ↔ 145 | By similarity |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 122 – 123 | Cleavage; by CORIN1 Publication | 2 | |
Sitei | 129 – 130 | Cleavage; by MMEBy similarity | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, PhosphoproteinProteomic databases
PaxDbi | P05125 |
PeptideAtlasi | P05125 |
PRIDEi | P05125 |
ProteomicsDBi | 296035 |
PTM databases
iPTMneti | P05125 |
PhosphoSitePlusi | P05125 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000041616, Expressed in cardiac atrium and 127 other tissues |
Genevisiblei | P05125, MM |
Interactioni
Subunit structurei
GO - Molecular functioni
- hormone activity Source: MGI
- hormone receptor binding Source: MGI
- neuropeptide hormone activity Source: MGI
- neuropeptide receptor binding Source: MGI
- signaling receptor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 231051, 1 interactor |
IntActi | P05125, 3 interactors |
STRINGi | 10090.ENSMUSP00000099520 |
Miscellaneous databases
RNActi | P05125, protein |
Structurei
3D structure databases
AlphaFoldDBi | P05125 |
BMRBi | P05125 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 76 – 106 | DisorderedSequence analysisAdd BLAST | 31 | |
Regioni | 146 – 150 | Important for degradation of atrial natriuretic peptide by IDEBy similarity | 5 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502S9RQ, Eukaryota |
GeneTreei | ENSGT00940000154513 |
HOGENOMi | CLU_144536_0_0_1 |
InParanoidi | P05125 |
OMAi | LSEVPPW |
OrthoDBi | 1596502at2759 |
TreeFami | TF106304 |
Family and domain databases
InterProi | View protein in InterPro IPR000663, Natr_peptide IPR030480, Natr_peptide_CS IPR002407, Natriuretic_peptide_atrial |
Pfami | View protein in Pfam PF00212, ANP, 1 hit |
PRINTSi | PR00711, ANATPEPTIDE PR00710, NATPEPTIDES |
SMARTi | View protein in SMART SM00183, NAT_PEP, 1 hit |
PROSITEi | View protein in PROSITE PS00263, NATRIURETIC_PEPTIDE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MGSFSITLGF FLVLAFWLPG HIGANPVYSA VSNTDLMDFK NLLDHLEEKM
60 70 80 90 100
PVEDEVMPPQ ALSEQTEEAG AALSSLPEVP PWTGEVNPPL RDGSALGRSP
110 120 130 140 150
WDPSDRSALL KSKLRALLAG PRSLRRSSCF GGRIDRIGAQ SGLGCNSFRY
RR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 96 – 97 | LG → SR in AAA37235 (PubMed:6542248).Curated | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | K02781 Genomic DNA Translation: AAA37235.1 AK147180 mRNA Translation: BAE27742.1 AL714013 Genomic DNA No translation available. CU210867 Genomic DNA No translation available. CH466594 Genomic DNA Translation: EDL14792.1 BC089615 mRNA Translation: AAH89615.1 |
CCDSi | CCDS18927.1 |
PIRi | A29370, AWMS |
RefSeqi | NP_032751.1, NM_008725.3 |
Genome annotation databases
Ensembli | ENSMUST00000103230; ENSMUSP00000099520; ENSMUSG00000041616 |
GeneIDi | 230899 |
KEGGi | mmu:230899 |
UCSCi | uc008vtq.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | K02781 Genomic DNA Translation: AAA37235.1 AK147180 mRNA Translation: BAE27742.1 AL714013 Genomic DNA No translation available. CU210867 Genomic DNA No translation available. CH466594 Genomic DNA Translation: EDL14792.1 BC089615 mRNA Translation: AAH89615.1 |
CCDSi | CCDS18927.1 |
PIRi | A29370, AWMS |
RefSeqi | NP_032751.1, NM_008725.3 |
3D structure databases
AlphaFoldDBi | P05125 |
BMRBi | P05125 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 231051, 1 interactor |
IntActi | P05125, 3 interactors |
STRINGi | 10090.ENSMUSP00000099520 |
PTM databases
iPTMneti | P05125 |
PhosphoSitePlusi | P05125 |
Proteomic databases
PaxDbi | P05125 |
PeptideAtlasi | P05125 |
PRIDEi | P05125 |
ProteomicsDBi | 296035 |
Protocols and materials databases
Antibodypediai | 13911, 752 antibodies from 40 providers |
Genome annotation databases
Ensembli | ENSMUST00000103230; ENSMUSP00000099520; ENSMUSG00000041616 |
GeneIDi | 230899 |
KEGGi | mmu:230899 |
UCSCi | uc008vtq.1, mouse |
Organism-specific databases
CTDi | 4878 |
MGIi | MGI:97367, Nppa |
VEuPathDBi | HostDB:ENSMUSG00000041616 |
Phylogenomic databases
eggNOGi | ENOG502S9RQ, Eukaryota |
GeneTreei | ENSGT00940000154513 |
HOGENOMi | CLU_144536_0_0_1 |
InParanoidi | P05125 |
OMAi | LSEVPPW |
OrthoDBi | 1596502at2759 |
TreeFami | TF106304 |
Enzyme and pathway databases
Reactomei | R-MMU-5578768, Physiological factors |
Miscellaneous databases
BioGRID-ORCSi | 230899, 6 hits in 72 CRISPR screens |
PROi | PR:P05125 |
RNActi | P05125, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000041616, Expressed in cardiac atrium and 127 other tissues |
Genevisiblei | P05125, MM |
Family and domain databases
InterProi | View protein in InterPro IPR000663, Natr_peptide IPR030480, Natr_peptide_CS IPR002407, Natriuretic_peptide_atrial |
Pfami | View protein in Pfam PF00212, ANP, 1 hit |
PRINTSi | PR00711, ANATPEPTIDE PR00710, NATPEPTIDES |
SMARTi | View protein in SMART SM00183, NAT_PEP, 1 hit |
PROSITEi | View protein in PROSITE PS00263, NATRIURETIC_PEPTIDE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ANF_MOUSE | |
Accessioni | P05125Primary (citable) accession number: P05125 Secondary accession number(s): Q5FW59 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 13, 1987 |
Last sequence update: | October 3, 2012 | |
Last modified: | May 25, 2022 | |
This is version 166 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families