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Protein

Natriuretic peptides A

Gene

NPPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hormone playing a key role in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. Also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus. Specifically binds and stimulates the cGMP production of the NPR1 receptor. Binds the clearance receptor NPR3.1 Publication

GO - Molecular functioni

  • hormone receptor binding Source: UniProtKB
  • neuropeptide hormone activity Source: BHF-UCL
  • neuropeptide receptor binding Source: BHF-UCL
  • peptide hormone receptor binding Source: Ensembl
  • receptor binding Source: UniProtKB

GO - Biological processi

  • cardiac muscle hypertrophy in response to stress Source: Ensembl
  • cell growth involved in cardiac muscle cell development Source: Ensembl
  • cellular protein metabolic process Source: Reactome
  • cellular response to mechanical stimulus Source: Ensembl
  • cGMP biosynthetic process Source: UniProtKB
  • female pregnancy Source: UniProtKB
  • negative regulation of cell growth Source: Ensembl
  • negative regulation of collecting lymphatic vessel constriction Source: Ensembl
  • negative regulation of systemic arterial blood pressure Source: Ensembl
  • neuropeptide signaling pathway Source: BHF-UCL
  • positive regulation of cardiac muscle contraction Source: BHF-UCL
  • positive regulation of delayed rectifier potassium channel activity Source: BHF-UCL
  • positive regulation of heart rate Source: BHF-UCL
  • positive regulation of potassium ion export across plasma membrane Source: BHF-UCL
  • protein folding Source: CAFA
  • receptor guanylyl cyclase signaling pathway Source: UniProtKB
  • regulation of atrial cardiac muscle cell membrane repolarization Source: BHF-UCL
  • regulation of blood pressure Source: UniProtKB
  • regulation of blood vessel size Source: UniProtKB-KW
  • regulation of calcium ion transmembrane transport via high voltage-gated calcium channel Source: BHF-UCL
  • regulation of cardiac conduction Source: Reactome
  • regulation of high voltage-gated calcium channel activity Source: BHF-UCL
  • response to hypoxia Source: Ensembl
  • response to insulin Source: Ensembl
  • response to muscle stretch Source: BHF-UCL
  • transcription initiation from RNA polymerase II promoter Source: Reactome

Keywordsi

Molecular functionHormone, Vasoactive

Enzyme and pathway databases

ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.
R-HSA-977225. Amyloid fiber formation.
SIGNORiP01160.

Names & Taxonomyi

Protein namesi
Recommended name:
Natriuretic peptides A
Alternative name(s):
CDD-ANF
Cardiodilatin
Short name:
CDD
Cardiodilatin-related peptide
Short name:
CDP
Prepronatriodilatin
Cleaved into the following chain:
Alternative name(s):
Atrial natriuretic peptide
Short name:
ANP
Gene namesi
Name:NPPA
Synonyms:ANP, PND
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000175206.10.
HGNCiHGNC:7939. NPPA.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Atrial standstill 2 (ATRST2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615745
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071307150R → Q in ATRST2. 1 Publication1
Atrial fibrillation, familial, 6 (ATFB6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:612201

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi123R → G: Loss of cleavage by CORIN. 1 Publication1

Keywords - Diseasei

Atrial fibrillation, Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi4878.
MalaCardsiNPPA.
MIMi612201. phenotype.
615745. phenotype.
Orphaneti1344. Atrial stand still.
334. Familial atrial fibrillation.
PharmGKBiPA256.

Chemistry databases

ChEMBLiCHEMBL1293193.

Polymorphism and mutation databases

BioMutaiNPPA.
DMDMi113864.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25By similarityAdd BLAST25
PropeptideiPRO_000000149326 – 123CuratedAdd BLAST98
PeptideiPRO_0000001494124 – 151Atrial natriuretic factor2 PublicationsAdd BLAST28

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi130 ↔ 1461 Publication

Post-translational modificationi

Cleaved by CORIN upon secretion to produce the functional hormone.2 Publications
Atrial natriuretic factor: Cleaved by MME. The cleavage initiates degradation of the factor and thereby regulate its activity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei123 – 124Cleavage; by CORIN1 Publication2
Sitei130 – 131Cleavage; by MME1 Publication2

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP01160.
PeptideAtlasiP01160.
PRIDEiP01160.

PTM databases

iPTMnetiP01160.
PhosphoSitePlusiP01160.

Miscellaneous databases

PMAP-CutDBiQ5JZE1.

Expressioni

Gene expression databases

BgeeiENSG00000175206.
CleanExiHS_NPPA.
ExpressionAtlasiP01160. baseline and differential.
GenevisibleiP01160. HS.

Organism-specific databases

HPAiHPA058269.

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • hormone receptor binding Source: UniProtKB
  • neuropeptide hormone activity Source: BHF-UCL
  • neuropeptide receptor binding Source: BHF-UCL
  • peptide hormone receptor binding Source: Ensembl
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110938. 50 interactors.
IntActiP01160. 5 interactors.
MINTiMINT-2861355.
STRINGi9606.ENSP00000365663.

Chemistry databases

BindingDBiP01160.

Structurei

Secondary structure

1153
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi139 – 141Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ANPNMR-A124-151[»]
1YK0X-ray2.40E129-149[»]
3N57X-ray3.03C/D124-151[»]
DisProtiDP00747.
ProteinModelPortaliP01160.
SMRiP01160.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01160.

Family & Domainsi

Sequence similaritiesi

Belongs to the natriuretic peptide family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IW5F. Eukaryota.
ENOG410ZUY6. LUCA.
HOGENOMiHOG000033937.
HOVERGENiHBG004227.
InParanoidiP01160.
KOiK12334.
PhylomeDBiP01160.
TreeFamiTF106304.

Family and domain databases

InterProiView protein in InterPro
IPR000663. Natr_peptide.
IPR030480. Natr_peptide_CS.
IPR002407. Natriuretic_peptide_atrial.
PfamiView protein in Pfam
PF00212. ANP. 1 hit.
PRINTSiPR00711. ANATPEPTIDE.
PR00710. NATPEPTIDES.
SMARTiView protein in SMART
SM00183. NAT_PEP. 1 hit.
PROSITEiView protein in PROSITE
PS00263. NATRIURETIC_PEPTIDE. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01160-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSFSTTTVS FLLLLAFQLL GQTRANPMYN AVSNADLMDF KNLLDHLEEK
60 70 80 90 100
MPLEDEVVPP QVLSEPNEEA GAALSPLPEV PPWTGEVSPA QRDGGALGRG
110 120 130 140 150
PWDSSDRSAL LKSKLRALLT APRSLRRSSC FGGRMDRIGA QSGLGCNSFR

YRR
Length:153
Mass (Da):16,708
Last modified:August 13, 1987 - v1
Checksum:iB38F03AA066A73EC
GO

Sequence cautioni

The sequence CAA15955 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti65E → D in AAA35529 (PubMed:3158606).Curated1

Polymorphismi

There are two different prepronatriodilatin alleles. One codes for 2 Arg residues at the C-terminus that are cleaved to form the mature peptide, while the other ends in a termination codon immediately after the last codon of the mature peptide.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01457932V → M. Corresponds to variant dbSNP:rs5063Ensembl.1
Natural variantiVAR_071307150R → Q in ATRST2. 1 Publication1
Natural variantiVAR_000594152 – 153Missing in allele 2. 2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02043 Genomic DNA. Translation: AAB59379.1.
M30262 mRNA. Translation: AAA35669.1.
X01470, X02558 Genomic DNA. Translation: CAA25699.1.
X01471 Genomic DNA. Translation: CAA25700.2.
M54951, M54947 Genomic DNA. Translation: AAA35529.1.
AL021155 Genomic DNA. Translation: CAA15955.2. Different initiation.
AL021155 Genomic DNA. Translation: CAI23398.1.
EU326308 Genomic DNA. Translation: ACA05916.1.
BC005893 mRNA. Translation: AAH05893.1.
K02399 Genomic DNA. Translation: AAA35528.1.
K02044 mRNA. Translation: AAA51730.1.
PIRiA22693. AWHU.
RefSeqiNP_006163.1. NM_006172.3.
UniGeneiHs.75640.

Genome annotation databases

EnsembliENST00000376480; ENSP00000365663; ENSG00000175206.
GeneIDi4878.
KEGGihsa:4878.
UCSCiuc001ati.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiANF_HUMAN
AccessioniPrimary (citable) accession number: P01160
Secondary accession number(s): Q13766, Q5JZE1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: November 22, 2017
This is version 188 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families