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Protein

Natriuretic peptides A

Gene

Nppa

Organism
Mus musculus (Mouse)
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 NPR3.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei122 – 1232Cleavage; by CORIN1 Publication
Sitei129 – 1302Cleavage; by MMEBy similarity

GO - Molecular functioni

  1. receptor binding Source: MGI

GO - Biological processi

  1. cardiac muscle hypertrophy in response to stress Source: MGI
  2. cellular response to mechanical stimulus Source: Ensembl
  3. cGMP biosynthetic process Source: UniProtKB
  4. female pregnancy Source: UniProtKB
  5. negative regulation of cell growth Source: Ensembl
  6. negative regulation of systemic arterial blood pressure Source: Ensembl
  7. receptor guanylyl cyclase signaling pathway Source: UniProtKB
  8. regulation of blood pressure Source: UniProtKB
  9. regulation of blood vessel size Source: UniProtKB-KW
  10. response to hypoxia Source: Ensembl
  11. response to insulin Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hormone, Vasoactive

Enzyme and pathway databases

ReactomeiREACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
REACT_198563. Amyloids.

Names & Taxonomyi

Protein namesi
Recommended name:
Natriuretic peptides A
Alternative name(s):
Prepronatriodilatin
Cleaved into the following 5 chains:
Alternative name(s):
Atrial natriuretic peptide
Short name:
ANP
Alternative name(s):
Atriopeptin I
Alternative name(s):
Atriopeptin II
Gene namesi
Name:Nppa
Synonyms:Pnd
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:97367. Nppa.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. extracellular space Source: MGI
  3. mast cell granule Source: Ensembl
  4. nucleus Source: Ensembl
  5. perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Mice display increased arterial blood pressure which is dietary salt intake independent. During pregnancy, increased blood pressure is observed, leading to late gestational proteinuria and smaller litters. Impaired trophoblast invasion and smaller spiral arteries are also observed in E12.5 embryos. In E18.5 embryos, mice display fewer trophoblasts and smaller arteries in the decidua and myometrium than those in wild-type mice.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi122 – 1221R → A: Abolishes maturation and cleavage by CORIN. 1 Publication
Mutagenesisi125 – 1251R → A: Does not affect maturation and cleavage by CORIN. 1 Publication
Mutagenesisi126 – 1261R → A: Does not affect maturation and cleavage by CORIN. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424By similarityAdd
BLAST
Propeptidei25 – 12298CuratedPRO_0000001495Add
BLAST
Peptidei123 – 15028Atrial natriuretic factor1 PublicationPRO_0000391784Add
BLAST
Peptidei126 – 15025Auriculin-BBy similarityPRO_0000001496Add
BLAST
Peptidei126 – 14924Auriculin-ABy similarityPRO_0000001497Add
BLAST
Peptidei127 – 14923Atriopeptin-1By similarityPRO_0000001498Add
BLAST
Peptidei127 – 14721Atriopeptin-2By similarityPRO_0000001499Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi129 ↔ 145By similarity

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.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

MaxQBiP05125.
PaxDbiP05125.
PRIDEiP05125.

PTM databases

PhosphoSiteiP05125.

Expressioni

Gene expression databases

CleanExiMM_NPPA.
GenevestigatoriP05125.

Interactioni

Protein-protein interaction databases

IntActiP05125. 4 interactions.
MINTiMINT-4087738.
STRINGi10090.ENSMUSP00000099520.

Structurei

3D structure databases

ProteinModelPortaliP05125.
SMRiP05125. Positions 121-148.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the natriuretic peptide family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG42244.
GeneTreeiENSGT00510000048659.
HOGENOMiHOG000033937.
HOVERGENiHBG004227.
InParanoidiP05125.
KOiK12334.
OMAiGCNSFRY.
OrthoDBiEOG7K9K4Q.
TreeFamiTF106304.

Family and domain databases

InterProiIPR000663. Natr_peptide.
IPR002407. Natriuretic_peptide_atrial.
[Graphical view]
PfamiPF00212. ANP. 1 hit.
[Graphical view]
PRINTSiPR00711. ANATPEPTIDE.
PR00710. NATPEPTIDES.
SMARTiSM00183. NAT_PEP. 1 hit.
[Graphical view]
PROSITEiPS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P05125-1 [UniParc]FASTAAdd to Basket

« Hide

        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
Length:152
Mass (Da):16,572
Last modified:October 3, 2012 - v2
Checksum:i1693D134B5FCA23D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti96 – 972LG → SR in AAA37235. (PubMed:6542248)Curated

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. Translation: CAM14483.1.
CU210867 Genomic DNA. Translation: CAQ52160.1.
CH466594 Genomic DNA. Translation: EDL14792.1.
BC089615 mRNA. Translation: AAH89615.1.
CCDSiCCDS18927.1.
PIRiA29370. AWMS.
RefSeqiNP_032751.1. NM_008725.2.
UniGeneiMm.482123.

Genome annotation databases

EnsembliENSMUST00000103230; ENSMUSP00000099520; ENSMUSG00000041616.
GeneIDi230899.
KEGGimmu:230899.
UCSCiuc008vtq.1. mouse.

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. Translation: CAM14483.1.
CU210867 Genomic DNA. Translation: CAQ52160.1.
CH466594 Genomic DNA. Translation: EDL14792.1.
BC089615 mRNA. Translation: AAH89615.1.
CCDSiCCDS18927.1.
PIRiA29370. AWMS.
RefSeqiNP_032751.1. NM_008725.2.
UniGeneiMm.482123.

3D structure databases

ProteinModelPortaliP05125.
SMRiP05125. Positions 121-148.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP05125. 4 interactions.
MINTiMINT-4087738.
STRINGi10090.ENSMUSP00000099520.

PTM databases

PhosphoSiteiP05125.

Proteomic databases

MaxQBiP05125.
PaxDbiP05125.
PRIDEiP05125.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000103230; ENSMUSP00000099520; ENSMUSG00000041616.
GeneIDi230899.
KEGGimmu:230899.
UCSCiuc008vtq.1. mouse.

Organism-specific databases

CTDi4878.
MGIiMGI:97367. Nppa.

Phylogenomic databases

eggNOGiNOG42244.
GeneTreeiENSGT00510000048659.
HOGENOMiHOG000033937.
HOVERGENiHBG004227.
InParanoidiP05125.
KOiK12334.
OMAiGCNSFRY.
OrthoDBiEOG7K9K4Q.
TreeFamiTF106304.

Enzyme and pathway databases

ReactomeiREACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
REACT_198563. Amyloids.

Miscellaneous databases

NextBioi380268.
PROiP05125.
SOURCEiSearch...

Gene expression databases

CleanExiMM_NPPA.
GenevestigatoriP05125.

Family and domain databases

InterProiIPR000663. Natr_peptide.
IPR002407. Natriuretic_peptide_atrial.
[Graphical view]
PfamiPF00212. ANP. 1 hit.
[Graphical view]
PRINTSiPR00711. ANATPEPTIDE.
PR00710. NATPEPTIDES.
SMARTiSM00183. NAT_PEP. 1 hit.
[Graphical view]
PROSITEiPS00263. NATRIURETIC_PEPTIDE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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].
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Heart.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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].
    Tissue: Heart.
  6. "Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP."
    John S.W., Veress A.T., Honrath U., Chong C.K., Peng L., Smithies O., Sonnenberg H.
    Am. J. Physiol. 271:R109-R114(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  7. "Processing of pro-atrial natriuretic peptide by corin in cardiac myocytes."
    Wu F., Yan W., Pan J., Morser J., Wu Q.
    J. Biol. Chem. 277:16900-16905(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, MUTAGENESIS OF ARG-122; ARG-125 AND ARG-126.
  8. "Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide-cyclic GMP signalling."
    Madhani M., Scotland R.S., MacAllister R.J., Hobbs A.J.
    Br. J. Pharmacol. 139:1289-1296(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Hypertension in mice lacking the proatrial natriuretic peptide convertase corin."
    Chan J.C., Knudson O., Wu F., Morser J., Dole W.P., Wu Q.
    Proc. Natl. Acad. Sci. U.S.A. 102:785-790(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING.
  10. "Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy."
    Cui Y., Wang W., Dong N., Lou J., Srinivasan D.K., Cheng W., Huang X., Liu M., Fang C., Peng J., Chen S., Wu S., Liu Z., Dong L., Zhou Y., Wu Q.
    Nature 484:246-250(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiANF_MOUSE
AccessioniPrimary (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: February 4, 2015
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.