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Symbol NPR1 contributors: mct/npt - updated : 26-03-2018
HGNC name natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A)
HGNC id 7943
Location 1q21.3      Physical location : 153.651.163 - 153.666.467
Synonym name
  • atrial natriuretic peptide
  • guanylate cyclase A
  • Synonym symbol(s) ANPRA, GUC2A, NPRA, ANPa, GUCY2A, ANP, GC-A
    EC.number 4.6.1.2
    DNA
    TYPE functioning gene
    STRUCTURE 15.30 kb     22 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    SPRR2C 1q21 small proline-rich protein 2C LOC149018 1q22 hypothetical LOC149018 LOC391102 1 similar to 60S acidic ribosomal protein P0 (L10E) LOR 1q21 loricrin PGLYRPIalpha 1q21 peptidoglycan recognition protein-I-alpha precursor PGLYRPIbeta 1q21 peptidoglycan recognition protein-I-beta precursor S100A9 1q21 S100 calcium binding protein A9 (calgranulin B) S100A12 1q21 S100 calcium binding protein A12 (calgranulin C) LOC391103 1 similar to lysosomal-associated transmembrane protein 4 beta; putative integral membrane transporter S100A8 1q21 S100 calcium binding protein A8 (calgranulin A) S100A15 1q22 S100 calcium binding protein A15 S100A7L2 1q22 S100 calcium binding protein A7-like 2 S100A7 1q21 S100 calcium binding protein A7 (psoriasin 1) S100A6 1q21 S100 calcium binding protein A6 (calcyclin) S100A5 1q21 S100 calcium binding protein A5 S100A4 1q21 S100 calcium binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog) LOC388700 1 hypothetical gene supported by BT006955; NM_002960 S100A2 1q21 S100 calcium binding protein A2 S100A1 1q21 S100 calcium binding protein A1 DKFZP547E1010 1q22 DKFZP547E1010 protein SNAPAP 1q22 SNAP-associated protein ILF2 1q21.1 interleukin enhancer binding factor 2, 45kDa NPR1 1q21.1 natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A) FLJ21919 1q22 hypothetical protein FLJ21919 SLC27A3 1q21.1 solute carrier family 27 (fatty acid transporter), member 3 LOC343052 1q22 similar to putative neuronal cell adhesion molecule P66beta 1q22 transcription repressor p66 beta component of the MeCP1 complex KIAA0476 1p36.13-q31.3 transcription repressor p66 beta component of the MeCP1 complex LOC200186 1q22 hypothetical protein LOC200186 SLC39A1 1q21 solute carrier family 39 (zinc transporter), member 1 CREB3L4 1q21.2 cAMP responsive element binding protein 3-like 4 JTB 1q21 jumping translocation breakpoint RAB13 12q13 RAB13, member RAS oncogene family RPS27 1q21 ribosomal protein S27 (metallopanstimulin 1) LOC91181 1q22 nuclear pore membrane glycoprotein 210-like
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 4201 - 1061 - 2008 18656450
    - - - - - ubiquiously expressed 2008 18656450
  • deletion of 17 AAs (Lys314–Gln330) in the membrane-distal part of the extracellular domain
  • has unique structural properties that impede ligand binding and ligand-induced guanylyl cyclase activity
  • can form heterodimers with wild type NPR1 thereby interfering with ANP signaling
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessels    
    Endocrineadrenal gland    
    Nervousnerve   highly
    Reproductivefemale systembreastmammary gland highly
    Respiratoryrespiratory tracttrachea  highly
    Urinarykidney    
    Visualeyeretinamacula   Rattus norvegicus
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Visualganglion cell Rattus norvegicus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • in pre-implantation embryos and in self-renewing sembryonic stem cells
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 450-AAs extracellular ligand-binding domain
  • a 21-AA hydrophobic membrane-spanning region
  • a 566-amino acid intracellular domain with intrinsic guanylate cyclase activity
  • a single transmembrane domain (TM), and an intracellular domain (ICD) exhibiting guanylyl cyclase activity
  • a protein kinase-like domain
  • seven sites of glycosylation
  • in addition to the GC domain, the kinase homology domain was also required for NPPA/NPR1 signaling
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to rattus Npr1
    ortholog to murine Npr1
    Homologene
    FAMILY
  • adenylyl cyclase class-4/guanylyl cyclase family
  • CATEGORY enzyme , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    text single-pass type I membrane protein
    basic FUNCTION
  • acting as a natriuretic peptide, receptor A
  • acting as a membrane guanylate cyclase GC-A
  • mediating vasorelaxant and natriuretic functions and decreasing aldosterone synthesis
  • involved in blood pressure regulation
  • involved in negative regulation of angiogenesis
  • playing a role in negative regulation of cell growth
  • involved in regulation of vasodilatation
  • NPR1 and PRKG2 are selectively induced in granulosa cells of preovulatory follicles by LH- and PR-dependent mechanisms, thereby providing a pathway for cGMP function during ovulation
  • critical roles in the control of fluid volume, blood pressure, cardiac remodeling, and other physiological functions and pathological states
  • role for NPR1 in the maintenance of self-renewal and pluripotency of ES cells
  • in cardiomyocytes from failing human hearts is refractory to NPPA stimulation
  • its renoprotective properties may result from the local inhibition of the renin-angiotensin-aldosterone system and oxidative stress in podocytes
  • 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
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS cardiovascular , excretion
    text
  • diuresis
  • PATHWAY
    metabolism nucleic
    signaling
  • cGMP biosynthesis
  • a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • Npr1 gene transcription is critically controlled by histone acetyltransferase EP300 and ETS1
  • specific receptor for atrial and brain natriuretic peptides (NPPA, NPPB)
  • PDE2A serves likely as the downstream transducer of cGMP signals produced by NPR1 activation
  • vasonatrin peptide stimulates both of the natriuretic peptide receptors, NPR1 and NPR2
  • 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
  • KLF10 acts as a transcriptional repressor of NPR1
  • 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
  • cell & other
    REGULATION
    Other responding to ANP (NPPA) and to a lesser degree to BNP
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal squamous cell carcinomas
    Susceptibility
  • to nephritis and progressive renal failure (see RFH1)
  • to hypertension
  • to myocardial infarction
  • development of left ventricular hypertrophy (LVH) in patients with hypertension
  • Variant & Polymorphism SNP , other
  • mutated in myocardial infarction
  • A2843G polymorphism in the promoter might be a genetic risk factor for the development of LVH in hypertension
  • Candidate gene
    Marker
  • potential prognostic marker in prostate cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    target for prostate cancer therapy
    ANIMAL & CELL MODELS
  • after 4 weeks of administering aldosterone and a high-salt diet, Gc-a knockout mice, but not wild-type mice, exhibited accelerated hypertension with massive proteinuria
  • disruption of Npr1 gene activates proinflammatory cytokines leading to fibrosis, hypertrophic growth, and remodeling of the kidneys of mutant mice