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FLASH GENE
Symbol PDE4A contributors: mct - updated : 06-02-2018
HGNC name phosphodiesterase 4A, cAMP-specific
HGNC id 8780
Location 19p13.2      Physical location : 10.531.332 - 10.580.307
Synonym name
  • cAMP-specific 3',5'-cyclic phosphodiesterase 4A
  • phosphodiesterase isozyme 4
  • cAMP-specific phosphodiesterase
  • phosphodiesterase 4A, cAMP-specific (dunce phosphodiesterase E2 dunce homolog, Drosophila)
  • Synonym symbol(s) DPDE2, PDE4
    EC.number 3.1.4.17/3.1.4.53
    DNA
    TYPE functioning gene
    STRUCTURE 48.98 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Physical map
    COL5A3 19p13.2 collagen, type V, alpha 3 RDH8 19p13.2-p13.3 retinol dehydrogenase 8 (all-trans) LOC388502 19 similar to Complement C3 precursor LOC388503 19 similar to Complement C3-1 LOC147740 19p13.2 similar to complement C3 protein (GPC3) precursor FLJ11286 19p13.2 hypothetical protein FLJ11286 ANGPTL6 19p13.2 angiopoietin-like 6 PPAN 19p13 peter pan homolog (Drosophila) P2RY11 19p13.2 purinergic receptor P2Y, G-protein coupled, 11 EIF3S4 19p13.2 eukaryotic translation initiation factor 3, subunit 4 delta, 44kDa DNMT1 19p13.2 DNA (cytosine-5-)-methyltransferase 1 EDG5 19p13.2 endothelial differentiation, sphingolipid G-protein-coupled receptor, 5 LOC388504 19 LOC388504 MRPL4 19p13.2 mitochondrial ribosomal protein L4 ICAM1 19p13.3-p13.2 intercellular adhesion molecule 1 (CD54), human rhinovirus receptor ICAM4 19p13.2-cen intercellular adhesion molecule 4, Landsteiner-Wiener blood group ICAM5 19p13.2 intercellular adhesion molecule 5, telencephalin LOC388505 MGC19604 19p13.2 similar to RIKEN cDNA B230118G17 gene RAVER1 19p13.2 RAVER1 ICAM3 19p13.3-p13.2 intercellular adhesion molecule 3 TYK2 19p13.2 tyrosine kinase 2 CDC37 19p13.2 CDC37 cell division cycle 37 homolog (S. cerevisiae) PDE4A 19p13.2 phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila) KEAP1 19p13.2 kelch-like ECH-associated protein 1 EDG8 19p13.2 endothelial differentiation, sphingolipid G-protein-coupled receptor, 8 AUTL4 19p13.2 AUT-like 4, cysteine endopeptidase (S. cerevisiae) FLJ12949 19p13.2 hypothetical protein FLJ12949 CDKN2D 19p13.2 cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) AP1M2 19p13.2 adaptor-related protein complex 1, mu 2 subunit CTL2 19p13.1 adaptor-related protein complex 1, mu 2 subunit ILF3 19p13 interleukin enhancer binding factor 3, 90kDa QTRT1 19p13.3 queuine tRNA-ribosyltransferase 1 (tRNA-guanine transglycosylase) DNM2 19p13.2 dynamin 2 IL1RL1LG 19p13.2 interleukin 1 receptor-like 1 ligand LOC255809 19p13.2 hypothetical LOC255809 CARM1 19p13.2 hypothetical LOC255809 MGC3262 19p13.2 hypothetical protein MGC3262
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 4794 - 886 widely 2017 27993970
  • isoform 1
  • interacting with LYN, ARRB2
  • cytoplasmic
  • 15 - 4503 - 825 - 2017 27993970
  • isoform 3, HSPDE4A10
  • - - 2091 - 686 - 2017 27993970
    10 - 4276 - 647 in normal pituitary 2017 27993970
  • PDE4A, isoform 4, PDE4A4
  • has propensity for association with membranes
  • - - 1770 - 323 widely expressed 2017 27993970
  • fails to hydrolyse cAMP
  • unique C-terminal region of PDE4A7 was unable to support an active catalytic unit, whereas its unique N-terminal region can
  • exclusively localized to the P1 particulate fraction in cells
  • 15 - 4608 126 860 widely expressed 2017 27993970
  • PDE4A11, isoform 2
  • unique, 81 amino acid N-terminal region
  • long isoform possessing UCR1 and UCR2 regulatory domains
  • interact with beta-arrestin, and weakly with LYN
  • activated by PKA phosphorylation and may contribute to compartmentalized cAMP signaling in cells in which it is expressed
  • cytoplasmic, ruffle membrane
  • - - 2707 - 864 . could be detected in discrete regions of brain, including the cerebellum, spinal cord and cerebral cortex . localized predominantly in the cytosol, but also associated with membrane fractions . in normal pituitary . mRNA was found to be expressed predominantly in skeletal muscle and brain 2017 27993970
  • PDE4A8
  • a novel N-terminal region of 85 amino acids that differs from those of the related 'long' PDE4A4, PDE4A10 and PDE4A11 isoforms
  • may have a specific function in regulating cAMP levels in human skeletal muscle and brain
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemovary  highly
     female systemplacenta   
     male systemprostate  highly
    Respiratorylung     Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    not specificfibroblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to Drosophila dunce gene
    homolog to murine Pde4a (85.6pc)
    homolog to rattus Pde4a (85.9pc)
    Homologene
    FAMILY cyclic nucleotide phosphodiesterase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • may downregulate cyclic AMP signaling at the cell membrane and/or in the extracellular space at the time of granule release
  • regulating the cellular concentrations of cyclic nucleotides and thereby playing a role in signal transduction
  • regulating the viability of medulloblastoma cells (Schmidt 2010)
  • widely expressed in brain tumors and promoting their growth and that inihibition with Rolipram overcomes tumor resistance and mediates tumor regression (Goldhoff 2008)
  • upregulation of PDE4A expression during cholestatic liver injury plays a potential pathogenic role in the development of inflammation, injury, and fibrosis
  • AKAP1-PRKACA-PDE4A distribution and integrity have a key role in cellular survival
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism purine/pyrimidine
    signaling signal transduction
    cAMP degradation
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • DISC1 regulates cyclic adenosine monophosphate (cAMP) signaling via interactions with PDE4
  • PDE4A inhibition regulates VCAM1 through a novel RAPGEF3-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury
  • PDE4A long isoforms can be phosphorylated by MAPKAPK2, which attenuates activation of such enzymes through their phosphorylation by protein kinase A
  • interaction with over-expressed AIP does not seem to affect PDE2A function, but the reported effect on PDE4A is, in contrast, reduced enzymatic activity
  • cell & other
    REGULATION
    inhibited by rolipram
    Other cleaved by caspase 3
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the striato-thalamo-cortical circuit, is associated with deficits of spatial working memory in patients with Parkinson disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • inhibition of PDE4A inhibition diminish proliferation of lung fibroblasts and therefore could be useful in the therapy of pathological remodeling in lung diseases (Selige 2010)
  • is reduced in cerebellar of patients with bipolar disorder and provides potential potential new therapeutic avenues for treatment of this disorder (Fatemi 2008)
  • ANIMAL & CELL MODELS