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FLASH GENE
Symbol NPPA contributors: mct/npt - updated : 12-01-2018
HGNC name natriuretic peptide precursor A
HGNC id 7939
Corresponding disease
ATFB6 atrial fibrillation, familial, 6
ATRST2 atrial standstill 2
Location 1p36.22      Physical location : 11.905.768 - 11.907.840
Synonym name
  • pronatriodilatin, cardionatrin
  • atropeptin/atrionatruretic factor
  • atrial natriuretic peptide
    • Synonym symbol(s) ANP, PND, ANF, CDD-ANF, ATFB6, ATRST2
    DNA
    TYPE functioning gene
    STRUCTURE 2.06 kb     3 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure promoter serving as target of cardiac-specific and stress-dependent gene regulation (TBX5, TAZ, YY1AP1)
    MAPPING cloned Y linked Y status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 858 - 101 - 2015 25260157
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartatrium  highly Homo sapiens
    Digestivesalivary glandparotid  highly Homo sapiensAdult
     salivary glandparotid  highly Homo sapiensFetal
    Nervousbrain   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • in the trabecular layer of the left ventricle and weakly expressed in the atrium and the trabecular layer of the right ventricle
  • in pre-implantation embryos and in self-renewing sembryonic stem cells
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal sequence
  • conserved 17-AAs disulfide-linked ring structure that is required for biological activity (Dickey 2009)
  • a region of homology to the porcine vasoactive peptide cardiodilatin and the atrial natriuretic factor (ANF) in the C terminal region
    • isoforms Precursor
    HOMOLOGY
    Homologene
    FAMILY
  • natriuretic peptide family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    basic FUNCTION
  • directly influencing blood pressure, body fluid homeostasis and kidney function
  • regulates sodium and water balance, blood pressure and myocardial mass through direct effects on the kidney, vasculature and heart and is involved in the pathophysiology of hypertension and heart failure
  • NPPB, NPPA, NPPC activate guanylyl cyclase suggesting a potential role in maintaining lens epithelial cell homeostasis (PMID;
  • regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation
  • regulates lipid metabolism and oxygen utilization in differentiated adipocytes by activating the alpha2 subunit of AMPK
  • enhances mitochondrial function as evidenced by increased oxygen consumption and induction of key mitochondrial genes
  • regulates lipid catabolism and enhances energy dissipation through AMPK activation in adipocytes
  • new function of corin and NPPA in promoting trophoblast invasion and spiral artery remodelling
  • profoundly inhibits evoked release of glutamate from the axonal terminals of medial habenula (MHb) to the interpeduncular nucleus (IPN) neurons
  • blocks neurotransmission by depleting presynaptic cAMP concentrations
  • might play a role in the differentiation of the parotid gland similarly as in brain and during fetal growth NPPA may play a role in the regulating the secretion of primitive salivary fluid, even if acini are still not developed
  • concerted action of NPPA and DRD1 to regulate sodium homeostasis in nephrotic syndrome
  • protective mechanism of NPPA against pathologic vascular hyperpermeability, suggesting a novel pharmacological intervention for the prevention of increased vascular leak via PAK1-dependent modulation of ARHGEF2 activity
  • early and specific marker for functional myocardium of the embryonic heart
  • importance of the endogenous NPPA/NPPB-NPR1 system not only in the neovascularization of ischemic tissues but also in embryonic vascular development and organ morphogenesis
  • importance of KLF10 and NPPA/NPR1 in exerting influences on chronic pulmonary disease pathogenesis
  • enhances endothelial barrier function by reducing RHOA activity and reorganizing the actin cytoskeleton
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • OSTN binds to NPR3 competitively with NPPA and may affect NPPA concentrations in a local or systemic manner
  • selective activation of the PRKAA2 by NPPA is essential for NPPA mediated lipolysis in adipocytes and has several important potential implications which are relevant to the role of NPPA in exercise, heart failure and obesity and insulin resistance
  • NKX2-5 and its responsive cis-regulatory DNA elements are essential for NPPA expression selectively in the developing heart
  • PDE2A plays an essential role in the NPPA effect on synaptic transmission
  • cooperative mechanism where ANXA6 potentiates NPPA-dependent counterhypertrophic responses in cardiomyocytes by facilitating regulated traffic of pro-NPPA
  • in the developing mammalian ventricles NPPA plays a local paracrine role in regulating the balance between cardiac progenitor cell (CPC) proliferation and differentiation via NPR1/cGMP-mediated signaling pathways
  • via its receptor, NPR1, NPPA maintains cardiovascular homeostasis by exerting diuretic, natriuretic, and hypotensive effects mediated, in part, by endothelial cells
  • CCM2 and PAK4 are important downstream mediators of NPPA/NPR1 signaling involved in cell spreading, an important initial step in the enhancement of endothelial barrier function
  • NSD3 decreases NPPA expression and, thereby, attenuates ISO-induced cardiomyocyte hypertrophy
    • cell & other
    REGULATION
    induced by CAMTA1, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA)
    ASSOCIATED DISORDERS
    corresponding disease(s) ATFB6 , ATRST2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in congestive heart failure
    Susceptibility
  • to nephropathy and microvascular damage in type 1 diabetes
  • to blood pressure variation
  • development of ischemic stroke
  • to cardioembolic stroke
    • Variant & Polymorphism other
  • polymorphism 2238C affect the course of nephropathy in inadequately controlled type 1 diabetic patients
  • common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension (Newton-Cheh 2009)
  • association between frequent nonsynonymous variant of NPPA and cardioembolic stroke
  • NPPA genetic polymorphism and serum NPPA levels may contribute to the development of ischemic stroke
    • Candidate gene
    Marker
  • NPPA genetic polymorphism and serum NPPA levels could be potential biomarkers for early detection of ischemic stroke
  • marker of heart failure in children with left ventricular volume overload
    • Therapy target
    ANIMAL & CELL MODELS
  • pregnant corin- or Nppa-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia