Human Gene NPPA (ENST00000376480.7) from GENCODE V44
  Description: Homo sapiens natriuretic peptide A (NPPA), mRNA. (from RefSeq NM_006172)
RefSeq Summary (NM_006172): The protein encoded by this gene belongs to the natriuretic peptide family. Natriuretic peptides are implicated in the control of extracellular fluid volume and electrolyte homeostasis. This protein is synthesized as a large precursor (containing a signal peptide), which is processed to release a peptide from the N-terminus with similarity to vasoactive peptide, cardiodilatin, and another peptide from the C-terminus with natriuretic-diuretic activity. Mutations in this gene have been associated with atrial fibrillation familial type 6. This gene is located adjacent to another member of the natriuretic family of peptides on chromosome 1. [provided by RefSeq, Oct 2015].
Gencode Transcript: ENST00000376480.7
Gencode Gene: ENSG00000175206.11
Transcript (Including UTRs)
   Position: hg38 chr1:11,845,709-11,847,783 Size: 2,075 Total Exon Count: 3 Strand: -
Coding Region
   Position: hg38 chr1:11,846,009-11,847,684 Size: 1,676 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:11,845,709-11,847,783)mRNA (may differ from genome)Protein (151 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ANF_HUMAN
DESCRIPTION: RecName: Full=Natriuretic peptides A; AltName: Full=CDD-ANF; AltName: Full=Prepronatriodilatin; Contains: RecName: Full=Cardiodilatin-related peptide; Short=CDP; Contains: RecName: Full=Atrial natriuretic factor; Short=ANF; AltName: Full=Atrial natriuretic peptide; Short=ANP; Flags: Precursor;
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.
SUBCELLULAR LOCATION: Secreted.
PTM: 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.
DISEASE: Defects in NPPA are the cause of familial atrial fibrillation 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.
SIMILARITY: Belongs to the natriuretic peptide family.
SEQUENCE CAUTION: Sequence=CAA15955.2; Type=Erroneous initiation;
WEB RESOURCE: Name=Wikipedia; Note=Atrial natriuretic peptide entry; URL="http://en.wikipedia.org/wiki/Atrial_natriuretic_peptide";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: NPPA
Diseases sorted by gene-association score: atrial standstill 2* (1229), atrial fibrillation, familial, 6* (919), nppa-related familial atrial fibrillation 6* (500), atrial standstill* (268), familial atrial fibrillation* (118), congestive heart failure (48), mitral valve disease (27), idiopathic edema (24), atrial fibrillation (22), heart disease (22), acute kidney failure (20), syndrome of inappropriate antidiuretic hormone (19), cirrhotic cardiomyopathy (17), renovascular hypertension (15), mitral valve stenosis (14), acute kidney tubular necrosis (14), syncope (12), mitral valve insufficiency (11), central sleep apnea (10), idiopathic hypercalciuria (10), progressive muscular dystrophy (10), hypertension, diastolic (10), pulmonary hypertension (10), liver cirrhosis (10), hepatorenal syndrome (9), tuberculous meningitis (9), hypoaldosteronism (9), myxedema (8), hyperaldosteronism (8), acute myocardial infarction (8), postural hypotension (8), malignant hypertension (8), multiple personality disorder (8), muscle hypertrophy (7), renal artery disease (7), pericardial effusion (7), acute poststreptococcal glomerulonephritis (7), conn's syndrome (7), korean hemorrhagic fever (6), vasculogenic impotence (6), aortic valve disease 2 (6), pure autonomic failure (5), hypertension, essential (5), hypoplastic left heart syndrome (5), kidney disease (4), dilated cardiomyopathy (3), myocardial infarction (3), tetralogy of fallot (2), pheochromocytoma (2), collagen disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 20974.30 RPKM in Heart - Atrial Appendage
Total median expression: 21115.43 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -17.9099-0.181 Picture PostScript Text
3' UTR -84.90300-0.283 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000663 - Natr_peptide
IPR002407 - Natriuretic_peptide_atrial

Pfam Domains:
PF00212 - Atrial natriuretic peptide

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1ANP - NMR 1YK0 - X-ray MuPIT 3N57 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P01160
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005102 receptor binding
GO:0005179 hormone activity
GO:0005184 neuropeptide hormone activity
GO:0005515 protein binding
GO:0051427 hormone receptor binding
GO:0051428 peptide hormone receptor binding
GO:0071855 neuropeptide receptor binding

Biological Process:
GO:0001666 response to hypoxia
GO:0003085 negative regulation of systemic arterial blood pressure
GO:0006182 cGMP biosynthetic process
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0006457 protein folding
GO:0007168 receptor guanylyl cyclase signaling pathway
GO:0007218 neuropeptide signaling pathway
GO:0007565 female pregnancy
GO:0008217 regulation of blood pressure
GO:0010460 positive regulation of heart rate
GO:0010469 regulation of receptor activity
GO:0014898 cardiac muscle hypertrophy in response to stress
GO:0030308 negative regulation of cell growth
GO:0032868 response to insulin
GO:0035994 response to muscle stretch
GO:0044267 cellular protein metabolic process
GO:0050880 regulation of blood vessel size
GO:0060372 regulation of atrial cardiac muscle cell membrane repolarization
GO:0060452 positive regulation of cardiac muscle contraction
GO:0061049 cell growth involved in cardiac muscle cell development
GO:0071260 cellular response to mechanical stimulus
GO:1901841 regulation of high voltage-gated calcium channel activity
GO:1902261 positive regulation of delayed rectifier potassium channel activity
GO:1902514 regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
GO:1903595 positive regulation of histamine secretion by mast cell
GO:1903766 positive regulation of potassium ion export across plasma membrane
GO:1903779 regulation of cardiac conduction
GO:1903815 negative regulation of collecting lymphatic vessel constriction

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0031012 extracellular matrix
GO:0032991 macromolecular complex
GO:0042629 mast cell granule
GO:0048471 perinuclear region of cytoplasm


-  Descriptions from all associated GenBank mRNAs
  E00562 - CDNA encoding gamma human atrium natriuretic polypeptide.
E05725 - gamma-hANP gene.
BC005893 - Homo sapiens natriuretic peptide precursor A, mRNA (cDNA clone MGC:14467 IMAGE:4273949), complete cds.
M30262 - Human cardiodilatin-atrial natriuretic factor (CDD-ANF) mRNA, complete cds.
JD221501 - Sequence 202525 from Patent EP1572962.
JD546147 - Sequence 527171 from Patent EP1572962.
JD268100 - Sequence 249124 from Patent EP1572962.
JD252749 - Sequence 233773 from Patent EP1572962.
JD426423 - Sequence 407447 from Patent EP1572962.
E00468 - cDNA coding for cardionatrin.
E01124 - cDNA coding human cardionatrin precursor.
JD242051 - Sequence 223075 from Patent EP1572962.
JD040037 - Sequence 21061 from Patent EP1572962.
JD175478 - Sequence 156502 from Patent EP1572962.
K02044 - Human prepronatriodilatin gene, atrial natriuretic factor coding region.
AB528342 - Synthetic construct DNA, clone: pF1KE0902, Homo sapiens NPPA gene for natriuretic peptide precursor A, without stop codon, in Flexi system.
KJ897262 - Synthetic construct Homo sapiens clone ccsbBroadEn_06656 NPPA gene, encodes complete protein.
KR710208 - Synthetic construct Homo sapiens clone CCSBHm_00010347 NPPA (NPPA) mRNA, encodes complete protein.
DQ893115 - Synthetic construct clone IMAGE:100005745; FLH193874.01X; RZPDo839C1279D natriuretic peptide precursor A (NPPA) gene, encodes complete protein.
DQ896389 - Synthetic construct Homo sapiens clone IMAGE:100010849; FLH193870.01L; RZPDo839C1269D natriuretic peptide precursor A (NPPA) gene, encodes complete protein.
EU176780 - Synthetic construct Homo sapiens clone IMAGE:100011669; FLH264107.01L; RZPDo839E08257D natriuretic peptide precursor A (NPPA) gene, encodes complete protein.
E01044 - cDNA encoding human cardiodilatin.
E01558 - cDNA encoding atrial vasodilatin-like protein of human heart.
E01583 - cDNA encoding human atrial vasodilatin-like peptide.
JD444982 - Sequence 426006 from Patent EP1572962.
JD168993 - Sequence 150017 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04270 - Vascular smooth muscle contraction

BioCarta from NCI Cancer Genome Anatomy Project
h_alkPathway - ALK in cardiac myocytes
h_gcrPathway - Corticosteroids and cardioprotection
h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart)

Reactome (by CSHL, EBI, and GO)

Protein P01160 (Reactome details) participates in the following event(s):

R-HSA-5578783 CORIN(802-1042) hydrolyses NPPA to form NPPA(124-151)
R-HSA-6784598 NPPA(124-151) binds NPR1
R-HSA-5578768 Physiological factors
R-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5576891 Cardiac conduction
R-HSA-212436 Generic Transcription Pathway
R-HSA-397014 Muscle contraction
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-977225 Amyloid fiber formation
R-HSA-74160 Gene expression (Transcription)
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: ANF_HUMAN, ANP, ENST00000376480.1, ENST00000376480.2, ENST00000376480.3, ENST00000376480.4, ENST00000376480.5, ENST00000376480.6, NM_006172, P01160, PND, Q13766, Q5JZE1, uc001ati.1, uc001ati.2, uc001ati.3, uc001ati.4
UCSC ID: ENST00000376480.7
RefSeq Accession: NM_006172
Protein: P01160 (aka ANF_HUMAN)
CCDS: CCDS139.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.