Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P01160 (ANF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Natriuretic peptides A
Alternative name(s):
CDD-ANF
Prepronatriodilatin

Cleaved into the following 2 chains:

  1. Cardiodilatin-related peptide
    Short name=CDP
  2. Atrial natriuretic factor
    Short name=ANF
    Alternative name(s):
    Atrial natriuretic peptide
    Short name=ANP
Gene names
Name:NPPA
Synonyms:ANP, PND
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length153 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.15

Subcellular location

Secreted.

Post-translational modification

Cleaved by CORIN upon secretion to produce the functional hormone.

Polymorphism

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.

Involvement in disease

Atrial fibrillation, familial, 6 (ATFB6) [MIM:612201]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20

Sequence similarities

Belongs to the natriuretic peptide family.

Sequence caution

The sequence CAA15955.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseAtrial fibrillation
   DomainSignal
   Molecular functionHormone
Vasoactive
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcGMP biosynthetic process

Inferred from direct assay Ref.15. Source: UniProtKB

cardiac muscle hypertrophy in response to stress

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from sequence or structural similarity. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

negative regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

negative regulation of systemic arterial blood pressure

Inferred from electronic annotation. Source: Ensembl

receptor guanylyl cyclase signaling pathway

Inferred from direct assay Ref.15. Source: UniProtKB

regulation of blood pressure

Inferred from direct assay Ref.12Ref.2. Source: UniProtKB

regulation of blood vessel size

Inferred from electronic annotation. Source: UniProtKB-KW

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentextracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: Ensembl

mast cell granule

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionreceptor binding

Inferred from direct assay Ref.15. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525
Peptide26 – 5530Cardiodilatin-related peptide
PRO_0000001492
Propeptide56 – 12368
PRO_0000001493
Peptide124 – 15128Atrial natriuretic factor Ref.12 Ref.13
PRO_0000001494

Sites

Site123 – 1242Cleavage; by CORIN

Amino acid modifications

Disulfide bond130 ↔ 146 Ref.19

Natural variations

Natural variant321V → M.
Corresponds to variant rs5063 [ dbSNP | Ensembl ].
VAR_014579
Natural variant152 – 1532Missing in allele 2.
VAR_000594

Experimental info

Mutagenesis1231R → G: Loss of cleavage by CORIN. Ref.16
Sequence conflict651E → D in AAA35529. Ref.6

Secondary structure

... 153
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01160 [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: B38F03AA066A73EC

FASTA15316,708
        10         20         30         40         50         60 
MSSFSTTTVS FLLLLAFQLL GQTRANPMYN AVSNADLMDF KNLLDHLEEK MPLEDEVVPP 

        70         80         90        100        110        120 
QVLSEPNEEA GAALSPLPEV PPWTGEVSPA QRDGGALGRG PWDSSDRSAL LKSKLRALLT 

       130        140        150 
APRSLRRSSC FGGRMDRIGA QSGLGCNSFR YRR 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of cDNA encoding a precursor for human atrial natriuretic polypeptide."
Oikawa S., Imai M., Ueno A., Tanaka S., Noguchi T., Nakazato H., Kangawa K., Fukuda A., Matsuo H.
Nature 309:724-726(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE 2).
[2]"mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria."
Nakayama K., Ohkubo H., Hirose T., Inayama S., Nakanishi S.
Nature 310:699-701(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE 2).
[3]"Gene structure of human cardiac hormone precursor, pronatriodilatin."
Nemer M., Chamberland M., Sirois D., Argentin S., Drouin J., Dixon R.A.F., Zivin R.A., Condra J.H.
Nature 312:654-656(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 2).
[4]"Nucleotide sequence of the gene encoding human atrial natriuretic factor precursor."
Greenberg B.D., Bencen G.H., Seilhamer J.J., Lewicki J.A., Fiddes J.C.
Nature 312:656-658(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 2).
[5]"Nucleotide sequences of the human and mouse atrial natriuretic factor genes."
Seidman C.E., Bloch K.D., Klein K.A., Smith J.A., Seidman J.G.
Science 226:1206-1209(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 2).
[6]"Molecular studies of the atrial natriuretic factor gene."
Seidman C.E., Bloch K.D., Zisfein J., Smit J., Haber E., Homcy C., Duby A.D., Choi E., Graham R.M., Seidman J.G.
Hypertension 7:I31-I34(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 2).
[7]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 2).
[8]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE 2).
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE 1).
Tissue: Prostate.
[10]"Cloning of genomic DNA for human atrial natriuretic factor."
Maki M., Parmentier M., Inagami T.
Biochem. Biophys. Res. Commun. 125:797-802(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75.
[11]"Molecular cloning and characterization of DNA sequences encoding rat and human atrial natriuretic factors."
Zivin R.A., Condra J.H., Dixon R.A.F., Seidah N.G., Chretien M., Nemer M., Chamberland M., Drouin J.
Proc. Natl. Acad. Sci. U.S.A. 81:6325-6329(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 118-153 (ALLELE 1).
[12]"Purification and complete amino acid sequence of alpha-human atrial natriuretic polypeptide (alpha-hANP)."
Kangawa K., Matsuo H.
Biochem. Biophys. Res. Commun. 118:131-139(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 124-151.
[13]"Hydrolysis of intact and Cys-Phe-cleaved human atrial natriuretic peptide in vitro by human tissue kallikrein."
Vanneste Y., Michel A., Deschodt-Lanckman M.
Eur. J. Biochem. 196:281-286(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 124-151.
[14]"Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera."
Bennett B.D., Bennett G.L., Vitangcol R.V., Jewett J.R., Burnier J., Henzel W., Lowe D.G.
J. Biol. Chem. 266:23060-23067(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR-BINDING.
[15]"Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP)."
Koller K.J., Lowe D.G., Bennett G.L., Minamino N., Kangawa K., Matsuo H., Goeddel D.V.
Science 252:120-123(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme."
Yan W., Wu F., Morser J., Wu Q.
Proc. Natl. Acad. Sci. U.S.A. 97:8525-8529(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING, MUTAGENESIS OF ARG-123.
[17]"Functional analysis of the transmembrane domain and activation cleavage of human corin: design and characterization of a soluble corin."
Knappe S., Wu F., Masikat M.R., Morser J., Wu Q.
J. Biol. Chem. 278:52363-52370(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING.
[18]"Solution conformation of an atrial natriuretic peptide variant selective for the type A receptor."
Fairbrother W.J., McDowell R.S., Cunningham B.C.
Biochemistry 33:8897-8904(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 124-151 MUTANT SELECTIVE FOR NPR-C RECEPTOR.
[19]"Structural determinants of natriuretic peptide receptor specificity and degeneracy."
He X.-L., Dukkipati A., Garcia K.C.
J. Mol. Biol. 361:698-714(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 129-149 IN COMPLEX WITH NPR3, DISULFIDE BOND.
[20]"Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation."
Hodgson-Zingman D.M., Karst M.L., Zingman L.V., Heublein D.M., Darbar D., Herron K.J., Ballew J.D., de Andrade M., Burnett J.C. Jr., Olson T.M.
N. Engl. J. Med. 359:158-165(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ATFB6.
+Additional computationally mapped references.

Web resources

Wikipedia

Atrial natriuretic peptide entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRAWHU. A22693.
RefSeqNP_006163.1. NM_006172.3.
UniGeneHs.75640.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ANPNMR-A124-151[»]
1YK0X-ray2.40E129-149[»]
3N57X-ray3.03C/D124-151[»]
DisProtDP00747.
ProteinModelPortalP01160.
SMRP01160. Positions 122-149.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110938. 10 interactions.
IntActP01160. 1 interaction.
MINTMINT-2861355.
STRING9606.ENSP00000365663.

Chemistry

BindingDBP01160.
ChEMBLCHEMBL1293193.

PTM databases

PhosphoSiteP01160.

Polymorphism databases

DMDM113864.

Proteomic databases

PaxDbP01160.
PRIDEP01160.

Protocols and materials databases

DNASU4878.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000376480; ENSP00000365663; ENSG00000175206.
GeneID4878.
KEGGhsa:4878.
UCSCuc001ati.3. human.

Organism-specific databases

CTD4878.
GeneCardsGC01M011909.
H-InvDBHIX0199955.
HGNCHGNC:7939. NPPA.
HPAHPA058269.
MIM108780. gene.
612201. phenotype.
neXtProtNX_P01160.
Orphanet334. Familial atrial fibrillation.
PharmGKBPA256.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42244.
HOGENOMHOG000033937.
HOVERGENHBG004227.
InParanoidP01160.
KOK12334.
OrthoDBEOG7K9K4Q.
PhylomeDBP01160.
TreeFamTF106304.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressP01160.
BgeeP01160.
CleanExHS_NPPA.
GenevestigatorP01160.

Family and domain databases

InterProIPR000663. Natr_peptide.
IPR002407. Natriuretic_peptide_atrial.
[Graphical view]
PfamPF00212. ANP. 1 hit.
[Graphical view]
PRINTSPR00711. ANATPEPTIDE.
PR00710. NATPEPTIDES.
SMARTSM00183. NAT_PEP. 1 hit.
[Graphical view]
PROSITEPS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01160.
GeneWikiAtrial_natriuretic_peptide.
GenomeRNAi4878.
NextBio18776.
PMAP-CutDBQ5JZE1.
PROP01160.
SOURCESearch...

Entry information

Entry nameANF_HUMAN
AccessionPrimary (citable) accession number: P01160
Secondary accession number(s): Q13766, Q5JZE1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: April 16, 2014
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM