P01160 (ANF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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	Familial atrial fibrillation 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 component	Secreted
Coding sequence diversity	Polymorphism
Disease	Atrial fibrillation
Domain	Signal
Molecular function	Hormone Vasoactive
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cGMP biosynthetic process Inferred from direct assay Ref.15. Source: UniProtKB cardiac muscle hypertrophy in response to stress Inferred from electronic annotation. Source: Compara female pregnancy Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from electronic annotation. Source: Compara 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 insulin stimulus Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: Compara mast cell granule Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
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 – 123

68

PRO_0000001493

Peptide

124 – 151

28

Atrial natriuretic factor Ref.12 Ref.13

PRO_0000001494

Sites

Site

123 – 124

2

Cleavage; by CORIN

Amino acid modifications

Disulfide bond

130 ↔ 146

Ref.19

Natural variations

Natural variant

32

1

V → M.
Corresponds to variant rs5063 [ dbSNP | Ensembl ].

VAR_014579

Natural variant

152 – 153

2

Missing in allele 2.

VAR_000594

Experimental info

Mutagenesis

123

1

R → G: Loss of cleavage by CORIN. Ref.16

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 [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] [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. , 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.

IPI

IPI00221279.

PIR

AWHU. A22693.

RefSeq

NP_006163.1. NM_006172.3.

UniGene

Hs.75640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ANP	NMR	-	A	124-151	[»]
1YK0	X-ray	2.40	E	129-149	[»]
3N57	X-ray	3.03	C/D	124-151	[»]

ProteinModelPortal

P01160.

SMR

P01160. Positions 122-149.

ModBase

Search...

Protein-protein interaction databases

IntAct

P01160. 1 interaction.

MINT

MINT-2861355.

STRING

9606.ENSP00000365663.

PTM databases

PhosphoSite

P01160.

Polymorphism databases

DMDM

113864.

Proteomic databases

PaxDb

P01160.

PRIDE

P01160.

Protocols and materials databases

DNASU

4878.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000376480; ENSP00000365663; ENSG00000175206.

GeneID

4878.

KEGG

hsa:4878.

UCSC

uc001ati.3. human.

Organism-specific databases

CTD

4878.

GeneCards

GC01M011909.

H-InvDB

HIX0199955.

HGNC

HGNC:7939. NPPA.

MIM

108780. gene.
612201. phenotype.

neXtProt

NX_P01160.

Orphanet

334. Familial atrial fibrillation.

PharmGKB

PA256.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42244.

HOGENOM

HOG000033937.

HOVERGEN

HBG004227.

InParanoid

P01160.

KO

K12334.

OrthoDB

EOG40K81J.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P01160.

Bgee

P01160.

CleanEx

HS_NPPA.

Genevestigator

P01160.

GermOnline

ENSG00000175206. Homo sapiens.

Family and domain databases

InterPro

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

Pfam

PF00212. ANP. 1 hit.
[Graphical view]

PRINTS

PR00711. ANATPEPTIDE.
PR00710. NATPEPTIDES.

SMART

SM00183. NAT_PEP. 1 hit.
[Graphical view]

PROSITE

PS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P01160.

ChEMBL

CHEMBL1293193.

EvolutionaryTrace

P01160.

GenomeRNAi

4878.

NextBio

18776.

PMAP-CutDB

Q5JZE1.

SOURCE

Search...

Entry information

Entry name

ANF_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 150 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.