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FLASH GENE
Symbol PDE4D contributors: mct - updated : 03-12-2018
HGNC name phosphodiesterase 4D, cAMP-specific
HGNC id 8783
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a variable N-terminus containing UCR1 and UCR2
  • a C-terminal catalytic core
  • mono polymer homomer , monomer , dimer
    HOMOLOGY
    interspecies homolog to Drosophila dunce gene
    ortholog to rattus Pde4d (98.1pc)
    ortholog to murine Pde4d (98.6pc)
    homolog to Drosophila dnc (64.6pc)
    Homologene
    FAMILY
  • cyclic nucleotide phosphodiesterase family
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    intracellular,nuclear envelope
    text
  • in the soluble fraction
  • associated with membranes
  • associated with the cytoskeleton and the centrosome
  • basic FUNCTION
  • cAMP specific nucleotide phosphodiesterase may be involved in signal transduction
  • playing a pivotal role in the regulation of airway smooth muscle relaxation by catalyzing the hydrolysis of cAMP
  • plays a critical role in the memory and hippocampal neurogenesis mediated by cAMP signaling
  • regulating the levels of cAMP in the cell
  • regulator of airway smooth-muscle contractility
  • cyclic nucleotide PDEs play important role in the achievement of meiotic competency by reducing intraoocyte cyclic nucleotides level in mammalian oocytes
  • role of PDE4D in BRAF-mutated melanoma as regulator of cell invasion
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism nucleic
    signaling signal transduction
    cyclic nucleotide metabolism
    a component
  • homodimer for the long isoforms
  • monomeric for isoforms with truncated N-termini
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
    two divalent metal cations per subunit :
  • Zn2+ (preferentially in site 1)
  • Mg2+ and/or Mn2+ (preferentially in site 2)
  • protein
  • RYR2 channel
  • upregulation of NOX4 leads to an upregulation of PDE4A, PDE4B, and PDE4D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis
  • PRKACA and PDE4D anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome
  • CC2D1A is a novel regulator of PDE4D
  • PDE4D interacts directly with Neuropilins, positive regulators of HH pathway
  • cell & other
    REGULATION
    activated by phosphatidic acid
    inhibited by rolipram
    ASSOCIATED DISORDERS
    corresponding disease(s) ACDS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    causing defective RyR2-channel function associated with heart failure and arrhythmias
    constitutional germinal mutation      
    are associated with ischemic stroke, due to increased cardiac risk factor as well as augmented risk of atrial fibrillation
    Susceptibility
  • to ischemic strocke
  • to asthma
  • Variant & Polymorphism SNP , other
  • polymorphism increasing the risk of cerebral infarction, exclusively to current smokers
  • SNPs associated with asthma
  • association between PDE4D polymorphism SNP83 and ischemic stroke
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    mental retardationother 
    CC2D1A and/or PDE4D may be promising targets for therapeutic interventions in many disorders with impaired PDE4D function
    cancerskin 
    potential as a target for preventing metastatic dissemination in melanomas
    cancerbrain 
    is a promising target to treat HH-related tumors
    ANIMAL & CELL MODELS
  • Pde4d-null mice exhibit reduced growth and midface hypoplasia
  • isolated Pde4d(-/-) murine cardiomyocytes showed increased whole-cell Ca2+ transient amplitudes and sarcoplasmic reticulum Ca2+content but unchanged L-type calcium current