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PDE4A Gene

protein-coding   GIFtS: 71
GCID: GC19P010527

Phosphodiesterase 4A, CAMP-Specific

(Previous names: phosphodiesterase 4A, cAMP-specific (dunce (Drosophila)-homolog...)
(Previous symbol: DPDE2)
  See PDE4A-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Phosphodiesterase 4A, CAMP-Specific1 2     Phosphodiesterase 4A, CAMP-Specific (Dunce2
DPDE21 2 3 5     Phosphodiesterase E2 Dunce Homolog, Drosophila2
PDE462 3     Phosphodiesterase Isozyme 42
Phosphodiesterase 4A, CAMP-Specific (Dunce (Drosophila)-Homolog
Phosphodiesterase E2)1
     EC 3.1.4.533
Phosphodiesterase E2 Dunce Homolog (Drosophila)1     EC 3.1.48
PDE42     EC 3.1.4.178
CAMP-Specific 3',5'-Cyclic Phosphodiesterase 4A2     

External Ids:    HGNC: 87801   Entrez Gene: 51412   Ensembl: ENSG000000659897   OMIM: 6001265   UniProtKB: P278153   

Export aliases for PDE4A gene to outside databases

Previous GC identifers: GC19P010663 GC19P010376 GC19P010392 GC19P010111


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for PDE4A Gene:
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4
subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of
cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein
plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding
different isoforms have been described for this gene.(provided by RefSeq, Jul 2011)

GeneCards Summary for PDE4A Gene:
PDE4A (phosphodiesterase 4A, cAMP-specific) is a protein-coding gene. Diseases associated with PDE4A include rubinstein-taybi syndrome. GO annotations related to this gene include cAMP binding and 3',5'-cyclic-AMP phosphodiesterase activity. An important paralog of this gene is PDE4D.

UniProtKB/Swiss-Prot: PDE4A_HUMAN, P27815
Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes

summary for PDE4A Gene:
Phosphodiesterases (PDEs) are a family of related phosphohydrolyases that selectively catalyze the
hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or
cGMP). They regulate the cellular levels, localization and duration of action of these second messengers by
controlling the rate of their degradation. There are 11 subtypes of PDEs, named PDE1-11; PDE4, 7 and 8
selectively degrade cAMP, PDE5, 6 and 9 selectively degrade cGMP and PDE1, 2, 3, 10 and 11 degrade both
cyclic nucleotides. PDEs are expressed ubiquitously, with each subtype having a specific tissue
distribution. These enzymes are involved in many signal transduction pathways and their functions include
vascular smooth muscle proliferation and contraction, cardiac contractility, platelet aggregation, hormone
secretion, immune cell activation, and they are involved in learning and memory.

Gene Wiki entry for PDE4A Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000019.10  NT_011295.12  NC_018930.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the PDE4A gene promoter:
         CREB   PPAR-gamma1   AP-1   PPAR-gamma2   C/EBPalpha   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): PDE4A promoter sequence
   Search Chromatin IP Primers for PDE4A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PDE4A


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.2   Ensembl cytogenetic band:  19p13.2   HGNC cytogenetic band: 19p13.2

PDE4A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PDE4A gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P010527:  view genomic region     (about GC identifiers)

Start:
10,527,449 bp from pter      End:
10,580,307 bp from pter
Size:
52,859 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: PDE4A_HUMAN, P27815 (See protein sequence)
Recommended Name: cAMP-specific 3',5'-cyclic phosphodiesterase 4A  
Size: 886 amino acids; 98143 Da
Cofactor: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a
preference for magnesium and/or manganese ions
Subunit: Isoform 1 interacts with LYN. Isoform 2 and isoform 6 interact weakly with LYN. Isoform 1, isoform 2 and
isoform 6 interact with ARRB2
3 PDB 3D structures from and Proteopedia for PDE4A:
2QYK (3D)        3I8V (3D)        3TVX (3D)    
Secondary accessions: O75522 O76092 Q16255 Q16691 Q5DM53 Q6PMT2 Q8IVA7 Q8WUQ3 Q9H3H2
Alternative splicing: 7 isoforms:  P27815-1   P27815-2   P27815-3   P27815-4   P27815-5   P27815-6   P27815-7   (Contains a phosphoserine at position 123)

Explore the universe of human proteins at neXtProt for PDE4A: NX_P27815

Explore proteomics data for PDE4A at MOPED

Post-translational modifications: 

  • Phosphorylation by MAPKAPK2 its activation through PKA phosphorylation (By similarity). Phosphorylated at Ser-686
    and Ser-688 when expressed in S.frugiperda cells. Isoform 2 and isoform 7 are activated by phosphorylation at
    Ser-119 and Ser-123 respectively by PKA1
  • Proteolytically cleaved by caspase-31
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for PDE4A (P27815) (see all 29)
     PIRIQQR  SVLENHH  IDMVLAT  SVSEMAS 


    See PDE4A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (5 alternative transcripts): 
    NP_001104777.1  NP_001104778.1  NP_001104779.1  NP_001230050.1  NP_006193.1  

    ENSEMBL proteins: 
     ENSP00000468507   ENSP00000270474   ENSP00000293683   ENSP00000394754   ENSP00000467137  
     ENSP00000341007   ENSP00000465792   ENSP00000370078  
    Reactome Protein details: P27815

    PDE4A Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for PDE4A
    OriGene MassSpec for PDE4A
    OriGene Custom Protein Services for PDE4A
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    Novus Biologicals PDE4A Protein
    Novus Biologicals PDE4A Lysates
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    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for PDE4A

     
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    PDE4A Antibody Products:

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    Abcam antibodies for PDE4A
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    LSBio Antibodies in human, mouse, rat for PDE4A

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    Search eBioscience for ELISAs for PDE4A 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    PDE: Phosphodiesterases

    IUPHAR Guide to PHARMACOLOGY protein family classification: PDE4A
    Phosphodiesterases, 3',5'-cyclic nucleotide

    4 InterPro protein domains:
     IPR002073 PDEase_catalytic_dom
     IPR023174 PDEase_CS
     IPR023088 PDEase
     IPR003607 HD/PDEase_dom

    Graphical View of Domain Structure for InterPro Entry P27815

    ProtoNet protein and cluster: P27815

    UniProtKB/Swiss-Prot: PDE4A_HUMAN, P27815
    Similarity: Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily


    Find genes that share domains with PDE4A           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: PDE4A_HUMAN, P27815
    Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
    Catalytic activity: Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate
    Enzyme regulation: Isoform 1, isoform 2, isoform 6 and isoform 7 are inhibited by rolipram and cilomilast. Isoform
    1, isoform 2 and isoform 6 are inhibited by 4-[(3-butoxy-4-methoxyphenyl)-methyl]-2-imidazolidinone (Ro 20-1724),
    roflumilast and denbufylline
    Biophysicochemical properties: Kinetic parameters: KM=4.0 uM for cAMP (isoform 2); KM=3 uM for cAMP (isoform 6);

         Genatlas biochemistry entry for PDE4A:
    cAMP specific nucleotide phosphodiesterase class IV,A,with homology to Drosophila dunce gene,involved in signal
    transduction

         Enzyme Numbers (IUBMB): EC 3.1.4.172 EC 3.1.4.531 EC 3.1.42

         Gene Ontology (GO): Selected molecular function terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003824catalytic activity ----
    GO:00041143',5'-cyclic-nucleotide phosphodiesterase activity ----
    GO:00041153',5'-cyclic-AMP phosphodiesterase activity IGI8413254
    GO:0005515protein binding IPI11306681
    GO:0030552cAMP binding IGI8413254
         
    Find genes that share ontologies with PDE4A           About GenesLikeMe


    Phenotypes:
         4 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Pde4a):
     cardiovascular system  immune system  nervous system  taste/olfaction 

    Find genes that share phenotypes with PDE4A           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for PDE4A: Pde4atm1Mct Pde4atm1.1Hazh

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for PDE4A
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for PDE4A
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for PDE4A

    miRNA
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    miRTarBase miRNAs that target PDE4A:
    hsa-mir-744-5p (MIRT037515), hsa-mir-335-5p (MIRT016809), hsa-mir-18a-3p (MIRT040823)

    Block miRNA regulation of human, mouse, rat PDE4A using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PDE4A (see all 55):
    hsa-miR-188-5p hsa-miR-1224-3p hsa-miR-139-5p hsa-miR-605 hsa-let-7a-2* hsa-miR-3138 hsa-miR-374a hsa-miR-374c
    SwitchGear 3'UTR luciferase reporter plasmidPDE4A 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for PDE4A
    Predesigned siRNA for gene silencing in human, mouse, rat PDE4A

    Gene Editing
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    GenScript: all cDNA clones in your preferred vector (see all 4): PDE4A (NM_001111308)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PDE4A
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PDE4A

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PDE4A


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    PDE4A_HUMAN, P27815: Isoform 1: Cytoplasm, perinuclear region
    PDE4A_HUMAN, P27815: Isoform 2: Cytoplasm, perinuclear region. Cell projection, ruffle membrane
    PDE4A_HUMAN, P27815: Isoform 4: Membrane; Peripheral membrane protein. Note=Isoform 4 has propensity for
    association with membranes
    PDE4A_HUMAN, P27815: Isoform 6: Cytoplasm, perinuclear region
    PDE4A_HUMAN, P27815: Isoform 7: Cytoplasm. Membrane. Note=Predominantly cytoplasmic
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytosol4
    extracellular2
    nucleus2
    cytoskeleton1
    mitochondrion1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm ----
    GO:0005829cytosol TAS--
    GO:0016020membrane TAS9677330
    GO:0032587ruffle membrane IEA--
    GO:0048471perinuclear region of cytoplasm IDA11306681

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    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for PDE4A About   (see all 11)  
    See pathways by source

    SuperPathContained pathways About
    1Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90
    2Sweet Taste Signaling
    Cellular Effects of Sildenafil0.46
    Sperm Motility0.37
    3Ca-dependent events
    Opioid Signalling0.54
    4Circadian entrainment
    Morphine addiction0.53
    5G Protein Signaling Pathways
    G Protein Signaling Pathways0.44


    Find genes that share SuperPaths with PDE4A           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for PDE4A
        Cellular Effects of Sildenafil
    Sperm Motility

    2 GeneGo (Thomson Reuters) Pathways for PDE4A
        G-protein signaling G-Protein alpha-s signaling cascades
    Signal transduction PKA signaling

    1 BioSystems Pathway for PDE4A
        G Protein Signaling Pathways

    2 Reactome Pathways for PDE4A
        DARPP-32 events
    G alpha (s) signalling events

    1 PharmGKB Pathway for PDE4A
        Beta-agonist/Beta-blocker Pathway, Pharmacodynamics

    2 Kegg Pathways  (Kegg details for PDE4A):
        Purine metabolism
    Morphine addiction

    UniProtKB/Swiss-Prot: PDE4A_HUMAN, P27815
    Pathway: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for PDE4A
    Interactions:

        GeneGlobe Interaction Network for PDE4A

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for PDE4A (P278152, 3 ENSP000002704744) via UniProtKB, MINT, STRING, and/or I2D (see all 104)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    AKAP6Q130233, ENSP000002809794I2D: score=1 STRING: ENSP00000280979
    PRKAR2AP138613, ENSP000002655634I2D: score=1 STRING: ENSP00000265563
    SQSTM1Q135013, ENSP000003744554I2D: score=1 STRING: ENSP00000374455
    AIPO001703, ENSP000002791464I2D: score=1 STRING: ENSP00000279146
    LYNP079483I2D: score=3 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006198cAMP catabolic process IMP17704206
    GO:0007165signal transduction IEA--
    GO:0007608sensory perception of smell IEA--
    GO:0010738regulation of protein kinase A signaling IEA--
    GO:0035690cellular response to drug IEA--

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    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for PDE4A available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CilostamidePDE3 inhibitor[68550-75-4]
    RolipramPDE4 inhibitor[61413-54-5]
    IBMXPDE inhibitor (non-selective)[28822-58-4]
    Sildenafil citrate Orally active, potent PDE5 inhibitor [171599-83-0]
    (R)-(-)-RolipramPDE4 inhibitor. More active enantiomer of rolipram (Cat. No. 0905)[85416-75-7]

    6 HMDB Compounds for PDE4A    About this table
    CompoundSynonyms CAS #PubMed Ids
    Adenosine monophosphate5'-AMP (see all 28)61-19-8--
    Cyclic AMPCyclic AMP (see all 19)60-92-4--
    Cyclic GMP3',5'-cyclic GMP (see all 13)7665-99-8--
    Guanosine monophosphate5'-GMP (see all 14)85-32-5--
    Theophylline1,3-Dimethylxanthine (see all 96)58-55-9--
    WaterDihydrogen oxide (see all 2)7732-18-5--

    Selected DrugBank Compounds for PDE4A (see all 15)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Enprofylline3-n-Propylxanthine (see all 4)41078-02-8targetinhibitor1885257 3446047 11752352 3002801 2262902 17670210
    DyphyllineDihydroxypropyl Theophylline (see all 8)479-18-5targetinhibitor7925603 17139284 11752352 225216 17016423
    OxtriphyllineCholine theophyllinate (see all 2)4499-40-5targetinhibitor12547256 12887610 15253881 15351234 12421478
    TheophyllineDimethylxanthine (see all 6)58-55-9targetinhibitor12547256 12887610 15253881 15351234 12421478
    Iloprost-- 78919-13-8targetinducer11551870 12952271 12441759 2461561
    Drotaverine-- 985-12-6targetinhibitor12823389 20554370 17502703
    Ibudilast2-Isopropyl-3-isobutyrylpyrazolo(1,5-a)pyridine (see all 18)50847-11-5targetinhibitor21036126 20124930 16313925
    KetotifenKetotifen Fumarate (see all 5)34580-14-8targetinhibitor1702263 16313925
    (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one-- --target--10592235
    4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid-- --target--10592235

    3 IUPHAR Ligands for PDE4A (PDE4A)    About this table
    LigandTypeActionAffinityPubmed IDs
    rolipram
    InhibitorInhibition99177268
    YM976
    InhibitorInhibition8.310991987
    Ro201724
    InhibitorInhibition6.59177268

    Selected Novoseek inferred chemical compound relationships for PDE4A gene (see all 124)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    rolipram 96.8 300 7559525 (4), 8651945 (4), 9218122 (3), 10640323 (3) (see all 99)
    roflumilast 96.1 112 19843061 (4), 19386793 (3), 16257550 (3), 17573446 (3) (see all 58)
    cilomilast 95.7 73 14561639 (3), 16424413 (3), 14636078 (2), 17155857 (2) (see all 45)
    piclamilast 92.3 21 15339393 (3), 15765929 (2), 9559883 (1), 10193778 (1) (see all 14)
    cdp 840 90.2 8 9218122 (1), 9163639 (1), 9405253 (1), 11044563 (1) (see all 8)
    8-((4-bromo-2,3-dioxobutyl)thio)-adenosine 3',5'-cyclic monophosphate 87.6 2 2160272 (1), 11863434 (1)
    cilostamide 85.8 15 1329900 (2), 9105766 (1), 1313303 (1), 9716350 (1) (see all 11)
    siguazodan 84.8 5 9223593 (1), 18788505 (1), 11044563 (1), 15265810 (1)
    motapizone 83.4 5 9154331 (2), 9559883 (1), 11834608 (1), 20082309 (1)
    zardaverine 81.3 1 11044563 (1)



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    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for PDE4A gene (5 alternative transcripts): 
    NM_001111307.1  NM_001111308.1  NM_001111309.1  NM_001243121.1  NM_006202.2  

    Unigene Cluster for PDE4A:

    Phosphodiesterase 4A, cAMP-specific
    Hs.89901  [show with all ESTs]
    Unigene Representative Sequence: NM_001111307
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000592685 ENST00000352831(uc002moj.2) ENST00000293683(uc002mok.2)
    ENST00000440014(uc002mol.2) ENST00000591971 ENST00000344979(uc002mom.2 uc002moo.2)
    ENST00000589073 ENST00000586275 ENST00000590407 ENST00000380702(uc021uow.1)

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate PDE4A (see all 55):
    hsa-miR-188-5p hsa-miR-1224-3p hsa-miR-139-5p hsa-miR-605 hsa-let-7a-2* hsa-miR-3138 hsa-miR-374a hsa-miR-374c
    SwitchGear 3'UTR luciferase reporter plasmidPDE4A 3' UTR sequence
    Inhib. RNA
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    Additional mRNA sequence: 

    AF073745.2 AY266362.1 AY593872.1 AY618547.1 BC019864.1 BC038234.1 L20965.1 M37744.1 
    S75213.1 U18087.1 U18088.1 U68532.1 U97584.1 

    9 DOTS entries:

    DT.208282  DT.75134232  DT.97812911  DT.100691695  DT.91866715  DT.92427218  DT.86844360  DT.121480539 
    DT.121480536 

    Selected AceView cDNA sequences (see all 108):

    AY593872 F31164 NM_006202 BQ052490 AW138155 AF073745 BQ446409 BF116176 
    U97584 BM021079 BM462182 BC038234 BQ009232 BU169201 AW296744 S75213 
    BM021314 BC019864 BQ961810 F37034 BQ672933 CR604925 BQ711857 BQ928991 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for PDE4A (see all 10)    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14a · 14b ^ 15 ^ 16 ^ 17a · 17b · 17c ^ 18a · 18b ^ 19a ·
    SP1:        -     -     -                                   -     -                       -                                   -                       -         
    SP2:                                                        -     -                       -                                   -                       -         
    SP3:              -     -                                   -     -                       -                                   -                       -         
    SP4:                                                                                      -                                   -                       -         
    SP5:                    -                                   -     -                                                                                             

    ExUns: 19b · 19c · 19d
    SP1:                  
    SP2:                  
    SP3:                  
    SP4:                  
    SP5:                  


    ECgene alternative splicing isoforms for PDE4A

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    PDE4A expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GTGCACTGTG
    PDE4A Expression
    About this image


    PDE4A expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 2 entries
             Metencephalon
     
     Gut Tube (Gastrointestinal Tract)
             Foregut
     
     Kidney (Urinary System)
             Metanephros
     
     Eye (Sensory Organs)
             Retina
    PDE4A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PDE4A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.89901

    UniProtKB/Swiss-Prot: PDE4A_HUMAN, P27815
    Tissue specificity: Isoform 1 is widely expressed. Isoform 2 is abundant in liver, stomach, testis, thyroid and
    adrenal glands. It is also found in placenta, kidney, pancreas, ovary, uterus, skin, monocytes, mast cells,
    macrophages, as well as in bronchial smooth muscle. Isoform 6 is expressed at high levels in the heart and small
    intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood
    lymphocytes. Isoform 7 is expressed predominantly in skeletal muscle and brain and at lower levels in the testis.
    Isoform 7 is expressed in the brain. Found in specific neuronal subpopulations in cortex, spinal cord and
    cerebellum (at protein level)

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of chordates.

    Orthologs for PDE4A gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Pde4a1 , 5 phosphodiesterase 4A, cAMP specific1, 5 82.05(n)1
    84.82(a)1
      9 (7.73 cM)5
    185771  NM_183408.31  NP_899668.11 
     211657145 
    lizard
    (Anolis carolinensis)
    Reptilia PDE4A6
    phosphodiesterase 4A, cAMP-specific
    75(a)
    1 ↔ 1
    2(28469915-28547520)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia LOC1004888461 cAMP-specific 3',5'-cyclic phosphodiesterase 4D-like 75.72(n)
    85.99(a)
      100488846  XM_004918856.1  XP_004918913.1 
    zebrafish
    (Danio rerio)
    Actinopterygii pde4a1 phosphodiesterase 4A, cAMP-specific 75.56(n)
    82.58(a)
      572061  XM_695720.5  XP_700812.5 


    ENSEMBL Gene Tree for PDE4A (if available)
    TreeFam Gene Tree for PDE4A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for PDE4A gene
    PDE4D2  PDE8B2  PDE4B2  PDE4C2  PDE7B2  PDE1B2  PDE1A2  PDE9A2  
    PDE1C2  PDE7A2  PDE8A2  
    6 SIMAP similar genes for PDE4A using alignment to 5 protein entries:     PDE4A_HUMAN (see all proteins):
    PDE4B    PDE8B    HSPDE4D    PDE4D    PDE4C    PDE1B

    Find genes that share paralogs with PDE4A           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for PDE4A (see all 1442)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1884544161,2
    C--10462175(+) AGTGAA/GCTGTG 1 -- us2k10--------
    rs1813511781,2
    --10462389(+) CCAGTC/GTCTAT 1 -- us2k10--------
    rs26339711,2
    C,F,A--10462402(-) ttctaT/Cttttt 1 -- us2k17Minor allele frequency- C:0.44NA WA CSA EA 365
    rs1842982741,2
    --10462456(+) GAACTA/GTTAGG 1 -- us2k10--------
    rs769251881,2
    C,F--10462515(+) ATTAAA/GAGCCT 1 -- us2k11Minor allele frequency- G:0.04EA 120
    rs1900575121,2
    C--10462618(+) CCCTCC/TTGCAG 1 -- us2k10--------
    rs1818083421,2
    --10462660(+) TAAATC/GTAATA 1 -- us2k10--------
    rs65116981,2
    C,F,A,H--10462668(+) ataaaT/Caaatt 1 -- us2k1 tfbs319Minor allele frequency- C:0.45NS EA NA WA CSA 2343
    rs1166933361,2
    F--10462676(+) ATTACA/GTAGTG 1 -- us2k11Minor allele frequency- G:0.04WA 118
    rs1872474231,2
    --10462723(+) GAAGTC/TCTAGG 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for PDE4A (10527449 - 10580307 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for PDE4A:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv833744CNV Loss17160897
    nsv911041CNV Loss21882294
    dgv3725n71CNV Loss21882294
    nsv521918CNV Gain19592680
    nsv518008CNV Gain19592680

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 600126    OMIM disorders: --

    1 disease for PDE4A:    
    About MalaCards
    rubinstein-taybi syndrome

    2 diseases from the University of Copenhagen DISEASES database for PDE4A:
    Chronic obstructive pulmonary disease     Asthma

    Find genes that share disorders with PDE4A           About GenesLikeMe

    Selected Novoseek inferred disease relationships for PDE4A gene (see all 62)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pulmonary disease chronic obstructive 76.4 84 11964752 (3), 18341675 (2), 19213793 (2), 16267357 (2) (see all 55)
    chronic obstructive asthma 65.6 9 15912967 (1), 16257373 (1), 10419856 (1), 17428447 (1) (see all 7)
    asthma 63.6 111 19135348 (4), 15639300 (3), 11964752 (3), 14636078 (2) (see all 66)
    inflammation 48.7 39 15607122 (2), 16469485 (2), 14580925 (2), 10372831 (2) (see all 29)
    airways disease 46.6 2 16861399 (1), 15765929 (1)
    dermatitis atopic 41.5 11 17355425 (2), 8752839 (2), 9338548 (1), 10419856 (1) (see all 8)
    necrosis 38.8 32 10193778 (2), 19256507 (2), 11996895 (2), 14561639 (1) (see all 21)
    leydig cell tumor 33.2 1 1713581 (1)
    asthma allergic 30.6 7 15665325 (3), 11590377 (2)
    leukemia lymphocytic chronic 29.4 10 12531792 (2), 11839681 (2), 15652238 (2), 17699872 (1) (see all 5)

    Genetic Association Database (GAD): PDE4A
    Human Genome Epidemiology (HuGE) Navigator: PDE4A (3 documents)

    Export disorders for PDE4A gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for PDE4A gene, integrated from 10 sources (see all 737):
    (articles sorted by number of sources associating them with PDE4A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK. (PubMed id 20196770)1, 2, 9 Li X....Baillie G.S. (Biochem. J. 2010)
    2. Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change. (PubMed id 18095939)1, 2, 9 Mackenzie K.F.... Bolger G.B. (Biochem. J. 2008)
    3. Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse. (PubMed id 8009369)1, 3, 9 Milatovich A....Francke U. (Somat. Cell Mol. Genet. 1994)
    4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    5. Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene. (PubMed id 15738310)1, 2 Wallace D.A.... Houslay M.D. (Mol. Pharmacol. 2005)
    6. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    7. An unappreciated role for RNA surveillance. (PubMed id 14759258)1, 2 Hillman R.T.... Brenner S.E. (Genome Biol. 2004)
    8. Purification and characterization of the human pde4a catalytic domain (pde4a(330-723)) expressed in sf9 cells. (PubMed id 11566027)1, 2 Lario P.I.... Huang Z. (Arch. Biochem. Biophys. 2001)
    9. Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic AMP-specific phosphodiesterase PDE4A10. (PubMed id 11306681)1, 2 Rena G.... Houslay M.D. (Mol. Pharmacol. 2001)
    10. Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase 4A variant RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2. (PubMed id 9677330)1, 2 Sullivan M.... Houslay M.D. (Biochem. J. 1998)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 5141 HGNC: 8780 AceView: PDE4A Ensembl:ENSG00000065989 euGenes: HUgn5141
    ECgene: PDE4A Kegg: 5141 H-InvDB: PDE4A

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for PDE4A Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for PDE4A gene:
    Search GeneIP for patents involving PDE4A

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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