Reviewed, UniProtKB/Swiss-Prot P01160 (ANF_HUMAN)

Names and origin

Protein names

Recommended name:
    Atrial natriuretic factor
      Short name=ANF
Alternative name(s):
    Atrial natriuretic peptide
      Short name=ANP
    Prepronatriodilatin
    CDD-ANF
Cleaved into the following chain:
    1- Recommended name:
            Cardiodilatin-related peptide
                Short name=CDP

Gene names

Name:	NPPA
Synonyms:	ANP, PND

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	153 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	A potent vasoactive substance which is thought to play a key role in cardiovascular homeostasis. Has a cGMP-stimulating activity.
Subunit structure	Interacts with NPR3.
Subcellular location	Secreted.
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	Defects in NPPA are the cause of atrial fibrillation familial type 6 (ATFB6) [MIM:612201]. Atrial fibrillation is a common disorder of cardiac rhythm that is hereditary in a small subgroup of patients. It is characterized by disorganized atrial electrical activity, progressive deterioration of atrial electromechanical function and ineffective pumping of blood into the ventricles. It can be associated with palpitations, syncope, thromboembolic stroke, and congestive heart failure. Ref.15
Sequence similarities	Belongs to the natriuretic peptide family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Atrial fibrillation
Domain	Signal
Molecular function	Hormone Vasoactive
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	regulation of blood pressure Ref.2 Ref.11 Inferred from direct assay. Source: UniProtKB regulation of blood vessel size Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB
Molecular function	hormone activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Peptide

26 – 55

30

Cardiodilatin-related peptide

PRO_0000001492

Propeptide

56 – 122

67

PRO_0000001493

Peptide

124 – 151

28

Atrial natriuretic factor Ref.11

PRO_0000001494

Amino acid modifications

Disulfide bond

130 ↔ 146

Ref.14

Natural variations

Natural variant

32

1

V → M: dbSNP rs5063.

VAR_014579

Natural variant

152 – 153

2

Missing in allele 2.

VAR_000594

Experimental info

Sequence conflict

65

1

E → D in AAA35529. Ref.6

Secondary structure

1

.

.

.

153

Helix Strand Turn

Details...

Beta strand

139 – 141

3

Sequences

	Sequence		Length	Mass (Da)
	P01160-1 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: B38F03AA066A73EC	FASTA	153	16,708
	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

References

	« Hide 'large scale' referencesShow '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: 6203042] [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: 6547996] [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: 6095118] [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: 6095119] [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: 6542248] [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: 3158606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 2).
[7]	"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. , 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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE 1). Tissue: Prostate.
[9]	"Cloning of genomic DNA for human atrial natriuretic factor." Maki M., Parmentier M., Inagami T. Biochem. Biophys. Res. Commun. 125:797-802(1984) [PubMed: 6097248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-75.
[10]	"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: 6238331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 118-153 (ALLELE 1).
[11]	"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: 6230082] [Abstract] Cited for: PROTEIN SEQUENCE OF 124-151.
[12]	"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: 1826098] [Abstract] Cited for: PROTEIN SEQUENCE OF 124-151.
[13]	"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: 8043577] [Abstract] Cited for: STRUCTURE BY NMR OF 124-151 MUTANT SELECTIVE FOR NPR-C RECEPTOR.
[14]	"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: 16870210] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 129-149 IN COMPLEX WITH NPR3, DISULFIDE BOND.
[15]	"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: 18614783] [Abstract] Cited for: INVOLVEMENT IN ATFB6.
+	Additional computationally mapped references.

Web resources

Wikipedia

Atrial natriuretic peptide entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
BC005893 mRNA. Translation: AAH05893.1.
K02399 Genomic DNA. Translation: AAA35528.1.
K02044 mRNA. Translation: AAA51730.1.

IPI

IPI00221279.

PIR

AWHU. A22693.

RefSeq

NP_006163.1.

UniGene

Hs.75640

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ANP	NMR	-	A	124-151	[»]
1YK0	X-ray	2.40	E	129-149	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P01160. 1 interaction.

Genome annotation databases

Ensembl

ENSG00000175206. Homo sapiens. [Contig view]

GeneID

4878.

KEGG

hsa:4878.

Organism-specific databases

GeneCards

GC01M011840.

H-InvDB

HIX0000130.

HGNC

HGNC:7939. NPPA.

MIM

108780. gene.
612201. phenotype.

PharmGKB

PA256.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P01160.

HOVERGEN

P01160.

Gene expression databases

ArrayExpress

P01160.

Bgee

P01160.

CleanEx

HS_NPPA.

GermOnline

ENSG00000175206. Homo sapiens.

Family and domain databases

InterPro

IPR002407. At__natriurtcpep.
IPR000663. Natr_peptide.
[Graphical view]

Pfam

PF00212. ANP. 1 hit.
[Graphical view]

PRINTS

PR00711. ANATPEPTIDE.
PR00710. NATPEPTIDES.

ProDom

PD005107. At__natriurtcpep. 1 hit.
PD005617. Natr_peptide. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00183. NAT_PEP. 1 hit.
[Graphical view]

PROSITE

PS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

18776.

SOURCE

Search...

Entry information

Entry name

ANF_HUMAN

Accession

Primary (citable) accession number: P01160
Secondary accession number(s): Q13766

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 13, 1987
Last modified:	May 5, 2009
This is version 112 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)