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FLASH GENE
Symbol PDE5A contributors: mct - updated : 12-07-2013
HGNC name phosphodiesterase 5A, cGMP-specific
HGNC id 8784
Location 4q26      Physical location : 120.415.551 - 120.549.981
Synonym name cGMP-binding cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase 5A
Synonym symbol(s) CGB-PDE, CN5A, PDE5, PDE5A1
EC.number 3.1.4.17/3.1.4.35
DNA
TYPE functioning gene
STRUCTURE 134.43 kb     21 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor
text structure
  • PDE5A2 intronic promoter upregulated by CAMP or CGMP
  • the weaker 182-bp PDE5A2 promoter is located between the A3- and A2-specific exons and contains an indispensable Sp1-binding sequence
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text three alternatively spliced isoforms (PDE5A1-3) that differ in the N-terminus (PMID: 17017938)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 7005 100 875 ubiquitous 2006 17017938
  • PDE5A1
  • 21 splicing 6836 - 833 ubiquitous 2006 17017938
  • PDE5A2
  • 21 splicing 6788 - 823 specific to smooth muscle 2006 17017938
    PDE5A3
    - splicing 3070 - 865 - 2006 17017938
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestiveliver    
    Endocrinepancreas    
     parathyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    Nervousbrain    
    Respiratorylung   highly
     respiratory tracttrachea  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Muscularmyocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two N terminal cGMP binding domains
  • a C terminal catalytic domain with two putative divalent metal sites, that hydrolyzes cGMP and a regulatory (R) domain that contains two GAFs (a and b), GAF domain present in phytochromes
  • HOMOLOGY
    Homologene
    FAMILY cyclic nucleotide phosphodiesterase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • localization of PDE5A at the level of caveolin-rich lipid rafts
  • basic FUNCTION
  • involved in signal transduction by regulating the intracellular concentration of cyclic nucleotides
  • modulating beta-adrenergic signaling
  • degrades cGMP in smooth muscle cells so as to maintain the contracted state of contractile organs such as the penis, blood vessels, uterus, and intestines
  • regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling
  • role in cardiomyocyte hypertrophy modulation
  • physiological role in restricting the effects of NOS3/GUCY1A3/PRKG signaling pathway to modulating beta-adrenergic stimulation via modulation of the L-type Ca(2+) current (I(Ca), while limiting effects on cardiac contraction
  • may play an important role in the growth of human malignant melanoma MAA cells
  • catalyzes the specific hydrolysis of cGMP to 5'- GMP
  • primary role of myocyte PDE5A regulation to myocardial pathobiology
  • inhibition of endothelial PDE5A improves endothelial function
  • potential role for PDE5A in erythrocytes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism nucleic
    signaling signal transduction
    cyclic nucleotide
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • zinc Zn2+
  • manganese Mn2+
  • magnesium Mg2+
  • cobalt Co2+
  • protein
    cell & other
    REGULATION
    inhibited by sildenafil (viagra)and by zaprinast
    Other regulated by the mitotic activity of the smooth muscle cells (SMCs)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in cardaiac failure
    constitutional       loss of function
    in priapism
    tumoral   translocation    
    aberration with recurrent breakpoints in Hodgkin lymphoma (HL), t(4;8)(q27;q24), which activate PDE5A and repress ZHX2, deregulating apoptosis, differentiation, and STAT1-signaling in HL cells
    constitutional       gain of function
    in hypertrophied and failing hearts
    Susceptibility
    Variant & Polymorphism repeat
    Candidate gene
    Marker
    Therapy target
  • SystemTypeDisorderPubmed
    cancer  
    PDE5A inhibitors could be used to elevate cGMP levels to induce RPSA-mediated, cancer-specific cell death
    reproductiongenital 
    for treating the priapism
    cardiovascularaquired 
    inhibition of PDE5A may be a new treatment strategy for cardiac hypertrophy and remodeling
    respiratorylung 
    PDE5A inhibitor as treatment of pulmonary hypertension
    ANIMAL & CELL MODELS