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PDE4D Gene

protein-coding   GIFtS: 71
GCID: GC05M058302

Phosphodiesterase 4D, CAMP-Specific

(Previous names: phosphodiesterase 4D, cAMP-specific (dunce (Drosophila)-homolog...)
(Previous symbol: DPDE3)
  See PDE4D-related diseases
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 4D, CAMP-Specific1 2     PDE4DN22
DPDE31 2 3 5     CAMP-Specific 3',5'-Cyclic Phosphodiesterase 4D2
PDE432 3     CAMP-Specific Phosphodiesterase PDE4D62
ACRDYS22 5     Phosphodiesterase 4D, CAMP-Specific (Phosphodiesterase E3 Dunce Homolog,
Drosophila)2
STRK12 5     EC 3.1.4.533
Phosphodiesterase 4D, CAMP-Specific (Dunce (Drosophila)-Homolog
Phosphodiesterase E3)1
     EC 3.1.48
Phosphodiesterase E3 Dunce Homolog (Drosophila)1     EC 3.1.4.178
HSPDE4D2     

External Ids:    HGNC: 87831   Entrez Gene: 51442   Ensembl: ENSG000001134487   OMIM: 6001295   UniProtKB: Q084993   

Export aliases for PDE4D gene to outside databases

Previous GC identifers: GC05M058430 GC05M059822 GC05M058237 GC05M058285 GC05M055222


(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 PDE4D Gene:
This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has
3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in
multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript
variants that encode functional proteins.(provided by RefSeq, Sep 2009)

GeneCards Summary for PDE4D Gene:
PDE4D (phosphodiesterase 4D, cAMP-specific) is a protein-coding gene. Diseases associated with PDE4D include acrodysostosis 2, with or without hormone resistance, and acrodysostosis 1, with or without hormone resistance. GO annotations related to this gene include ion channel binding and enzyme binding. An important paralog of this gene is PDE8B.

UniProtKB/Swiss-Prot: PDE4D_HUMAN, Q08499
Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes

summary for PDE4D 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 PDE4D 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 at NCBI GenBank:
NC_000005.9  NT_034772.7  NC_018916.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the PDE4D gene promoter:
         CREB   deltaCREB   Sox9   Nkx2-5   HNF-3beta   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidPDE4D promoter sequence
   Search Chromatin IP Primers for PDE4D

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat PDE4D


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

Entrez Gene cytogenetic band: 5q12   Ensembl cytogenetic band:  5q12.1   HGNC cytogenetic band: 5q12

PDE4D Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PDE4D gene location

GeneLoc information about chromosome 5         GeneLoc Exon Structure

GeneLoc location for GC05M058302:  view genomic region     (about GC identifiers)

Start:
58,264,865 bp from pter      End:
59,817,947 bp from pter
Size:
1,553,083 bases      Orientation:
minus 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., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: PDE4D_HUMAN, Q08499 (See protein sequence)
Recommended Name: cAMP-specific 3',5'-cyclic phosphodiesterase 4D  
Size: 809 amino acids; 91115 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: Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a
ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed
of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Isoform 5, isoform N3 and isoform 12
bind GNB2L1 via their unique N-terminus. Binds ARRB2. Interacts (via N-terminus region) with SHANK2 (via
proline-rich region); the interaction is increased in a PKA-dependent manner
Selected PDB 3D structures from and Proteopedia for PDE4D (see all 35):
1E9K (3D)        1MKD (3D)        1OYN (3D)        1PTW (3D)        1Q9M (3D)        1TB7 (3D)    
Secondary accessions: O43433 Q13549 Q13550 Q13551 Q7Z2L8 Q8IV84 Q8IVA9 Q8IVD2 Q8IVD3 Q96HL4
Q9HCX7
Alternative splicing: 12 isoforms:  Q08499-1   Q08499-2   Q08499-3   Q08499-4   Q08499-5   Q08499-6   Q08499-7   Q08499-8   
Q08499-9   Q08499-10   Q08499-11   Q08499-12   (Contains a phosphoserine at position 59. Contains a phosphoserine at position 63)

Explore the universe of human proteins at neXtProt for PDE4D: NX_Q08499

Explore proteomics data for PDE4D at MOPED

Post-translational modifications: 

  • Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through
    phosphorylation (By similarity). Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not
    isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-591
  • Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their
    inhibition by ERK phosphorylation1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for PDE4D (Q08499) (see all 36)
     NREWYQS  SVLENHH  QSTHVLL  VLATDMS 


    See PDE4D Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (9 alternative transcripts): 
    NP_001098101.1  NP_001159371.1  NP_001184147.1  NP_001184148.1  NP_001184149.1  NP_001184150.1  NP_001184151.1  NP_001184152.1  
    NP_006194.2  

    ENSEMBL proteins: 
     ENSP00000345502   ENSP00000353152   ENSP00000424852   ENSP00000351800   ENSP00000321739  
     ENSP00000425605   ENSP00000384806   ENSP00000423094   ENSP00000421013   ENSP00000308485  
     ENSP00000425917   ENSP00000423555   ENSP00000425910   ENSP00000421829   ENSP00000424281  
     ENSP00000442734  
    Reactome Protein details: Q08499

    PDE4D Human Recombinant Protein Products:

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    Novus Biologicals PDE4D Proteins
    Novus Biologicals PDE4D Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for PDE4D

     
    Search eBioscience for Proteins for PDE4D 

     
    antibodies-online proteins for PDE4D (6 products) 

     
    antibodies-online peptides for PDE4D

    PDE4D Antibody Products:

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    Abcam antibodies for PDE4D (P27815, Q08499)
    Cloud-Clone Corp. Antibodies for PDE4D
    ThermoFisher Antibody for PDE4D
    antibodies-online antibodies for PDE4D (69 products) 

    PDE4D Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for PDE4D
    Cloud-Clone Corp. CLIAs for PDE4D
    Search eBioscience for ELISAs for PDE4D 
    antibodies-online kits for PDE4D (23 products) 


    (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: PDE4D
    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 Q08499

    ProtoNet protein and cluster: Q08499

    UniProtKB/Swiss-Prot: PDE4D_HUMAN, Q08499
    Similarity: Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily


    Find genes that share domains with PDE4D           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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: PDE4D_HUMAN, Q08499
    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: Inhibited by rolipram. Activated by phosphatidic acid

         Genatlas biochemistry entry for PDE4D:
    cAMP specific nucleotide phosphodiesterase class IV,D,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 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:00041143',5'-cyclic-nucleotide phosphodiesterase activity NAS10913353
    GO:00041153',5'-cyclic-AMP phosphodiesterase activity IGI8413254
    GO:0005515protein binding IPI--
    GO:0008144drug binding IPI15938621
    GO:0019899enzyme binding ISS--
         
    Find genes that share ontologies with PDE4D           About GenesLikeMe


    Phenotypes:
         10 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Pde4d):
     cardiovascular system  cellular  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  mortality/aging  muscle  no phenotypic analysis  reproductive system 

    Find genes that share phenotypes with PDE4D           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for PDE4D: Pde4dtm1Mct Pde4dtm2Mct

       genOway: Develop your customized and physiologically relevant rodent model for PDE4D

    miRNA
    Products:
        
    miRTarBase miRNAs that target PDE4D:
    hsa-mir-16-5p (MIRT031849), hsa-mir-103a-3p (MIRT027087), hsa-mir-340-5p (MIRT019645), hsa-mir-19b-3p (MIRT031236), hsa-mir-7-5p (MIRT025858), hsa-mir-18a-5p (MIRT031356), hsa-mir-335-5p (MIRT018254)

    Block miRNA regulation of human, mouse, rat PDE4D using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate PDE4D (see all 188):
    hsa-miR-124* hsa-miR-579 hsa-miR-1273d hsa-miR-409-5p hsa-miR-3649 hsa-miR-4273 hsa-miR-92b hsa-miR-130b
    SwitchGear 3'UTR luciferase reporter plasmidPDE4D 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for PDE4D
    Predesigned siRNA for gene silencing in human, mouse, rat PDE4D

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for PDE4D

    Clone
    Products:
         
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    GenScript: all cDNA clones in your preferred vector (see all 9): PDE4D (NM_001165899)
    Sino Biological Human cDNA Clone for PDE4D
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for PDE4D
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PDE4D

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for PDE4D 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PDE4D


    (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
    PDE4D_HUMAN, Q08499: Apical cell membrane. Cytoplasm (By similarity). Membrane (By similarity). Cytoplasm,
    cytoskeleton (By similarity). Cytoplasm, cytoskeleton, microtubule organizing center, centrosome (By similarity).
    Note=Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the
    centrosome (By similarity). Colocalized with SHANK2 to the apical membrane of colonic crypt cells
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    cytoskeleton2
    extracellular1
    mitochondrion1
    nucleus1
    plasma membrane1

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005815microtubule organizing center IEA--
    GO:0005829cytosol TAS--
    GO:0005891colocalizes with voltage-gated calcium channel complex ISS--
    GO:0016020NOT membrane IDA9371713
    GO:0016324apical plasma membrane IEA--

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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 PDE4D About   (see all 13)  
    See pathways by source

    SuperPathContained pathways About
    1Ca-dependent events
    Opioid Signalling0.54
    Development Beta adrenergic receptors signaling via cAMP0.32
    2Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90
    3Regulation of CFTR activity norm and CF
    Regulation of CFTR activity norm and CF 0.38
    Regulation of CFTR gating normal and CF 0.00
    4Sweet Taste Signaling
    Cellular Effects of Sildenafil0.46
    Sperm Motility0.37
    5Circadian entrainment
    Morphine addiction0.53


    Find genes that share SuperPaths with PDE4D           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for PDE4D
        Cellular Effects of Sildenafil
    Sperm Motility

    4 GeneGo (Thomson Reuters) Pathways for PDE4D
        Regulation of CFTR gating (normal and CF)
    Development Beta-adrenergic receptors signaling via cAMP
    Signal transduction PKA signaling
    Regulation of CFTR activity (norm and CF)

    3 BioSystems Pathways for PDE4D
        Myometrial Relaxation and Contraction Pathways
    G Protein Signaling Pathways
    TSH signaling pathway


    2 Reactome Pathways for PDE4D
        DARPP-32 events
    G alpha (s) signalling events

    1 PharmGKB Pathway for PDE4D
        Beta-agonist/Beta-blocker Pathway, Pharmacodynamics

    2 Kegg Pathways  (Kegg details for PDE4D):
        Purine metabolism
    Morphine addiction

    UniProtKB/Swiss-Prot: PDE4D_HUMAN, Q08499
    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 PDE4D
    Interactions:

        GeneGlobe Interaction Network for PDE4D

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

    Selected Interacting proteins for PDE4D (Q084991, 2, 3 ENSP000003848064) via UniProtKB, MINT, STRING, and/or I2D (see all 107)

    InteractantInteraction Details
    GeneCardExternal ID(s)
    ARRB2P321212, 3, ENSP000002692604MINT-8042744 MINT-8041863 MINT-8041836 MINT-8042714 I2D: score=2 STRING: ENSP00000269260
    PRKACAP176122, 3, ENSP000003095914MINT-8042744 MINT-8041863 MINT-8041836 MINT-8042714 I2D: score=1 STRING: ENSP00000309591
    AKAP12Q029522, 3, ENSP000002533324MINT-2411838 I2D: score=1 STRING: ENSP00000253332
    RXFP1Q9HBX92, ENSP000003032484MINT-8042744 MINT-8041863 MINT-8041836 MINT-8042714 STRING: ENSP00000303248
    AKAP5P245882, ENSP000003156154MINT-8041863 MINT-8041836 STRING: ENSP00000315615
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002027regulation of heart rate ISS16213210
    GO:0006198cAMP catabolic process IMP19252089
    GO:0006939smooth muscle contraction IEA--
    GO:0007165signal transduction ----
    GO:0007568aging IEA--

    Find genes that share ontologies with PDE4D           About GenesLikeMe



    (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 drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Compounds for PDE4D 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]

    Selected HMDB Compounds for PDE4D (see all 19)    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--
    MagnesiumMagnesium (see all 2)7439-95-4--
    Manganesemanganese 7439-96-5--
    PA(16:0/16:0)Dipalmitoylphosphatidic acid (see all 25)7091-44-3--
    PA(16:0/18:1(11Z))PA(16:0/18:1n7) (see all 10)----
    PA(16:0/18:1(9Z))PA(16:0/18:1n9) (see all 10)----
    PA(16:0/18:2(9Z,12Z))PA(34:2) (see all 10)----

    Selected DrugBank Compounds for PDE4D (see all 21)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Iloprost-- 78919-13-8targetinducer11551870 12952271 12441759 2461561
    2-[3-(2-Hydroxy-1,1-Dihydroxymethyl-Ethylamino)-Propylamino]-2-Hydroxymethyl-Propane-1,3-Diol-- --target--17139284 17016423 10592235
    4-[3-(Cyclopentyloxy)-4-Methoxyphenyl]-2-Pyrrolidinone-- 61413-54-5target--17139284 17016423 10592235
    Cis-4-Cyano-4-[3-(Cyclopentyloxy)-4-Methoxyphenyl]Cyclohexanecarboxylic Acid-- 153259-65-5target--17139284 17016423 10592235
    DyphyllineDihydroxypropyl Theophylline (see all 8)479-18-5targetinhibitor7925603 17139284 17016423
    KetotifenKetotifen Fumarate (see all 5)34580-14-8targetinhibitor1702263 16313925
    Piclamilast-- 144035-83-6target--10592235 15765929
    Roflumilast-- 162401-32-3targetinhibitor10592235 17726343
    (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one-- --target--10592235
    1-(4-Aminophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl Ester-- --target--10592235

    2 IUPHAR Ligands for PDE4D (PDE4D)    About this table
    LigandTypeActionAffinityPubmed IDs
    rolipram
    InhibitorInhibition7.29177268
    Ro201724
    InhibitorInhibition6.29177268

    7 Novoseek inferred chemical compound relationships for PDE4D gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    rolipram 86.9 8 9720765 (2), 7559525 (2), 11839681 (2), 15659833 (1) (see all 5)
    cilomilast 79.9 1 15576036 (1)
    roflumilast 74.9 1 15576036 (1)
    ibmx 54.6 2 9515164 (1)
    forskolin 46.2 1 9003416 (1)
    cyclic amp 35.9 1 17016624 (1)
    isoproterenol 32 4 16030021 (2), 14500724 (1), 12552097 (1)

    1 PharmGKB related drug/compound annotation for PDE4D gene    About this table
    Drug/compound PharmGKB Annotation
    diureticsCA  



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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 PDE4D gene (9 alternative transcripts): 
    NM_001104631.1  NM_001165899.1  NM_001197218.1  NM_001197219.1  NM_001197220.1  NM_001197221.1  NM_001197222.1  NM_001197223.1  
    NM_006203.4  

    Unigene Cluster for PDE4D:

    Phosphodiesterase 4D, cAMP-specific
    Hs.117545  [show with all ESTs]
    Unigene Representative Sequence: NM_001197220
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 27):
    ENST00000340635(uc003jrs.2 uc003jrt.2 uc003jru.3 uc003jrv.2 uc003jrw.2 uc003jrx.2 uc003jry.3 uc003jrz.3 uc003jsa.2 uc003jsb.3)
    ENST00000360047 ENST00000507116 ENST00000358923 ENST00000317118 ENST00000503258
    ENST00000405755 ENST00000515011 ENST00000502484 ENST00000505453 ENST00000309641(uc010iwi.1)
    ENST00000405053 ENST00000502575(uc003jsc.3) ENST00000503947 ENST00000515324
    ENST00000514231 ENST00000512069 ENST00000509368(uc003jse.1 uc010iwj.2)

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate PDE4D (see all 188):
    hsa-miR-124* hsa-miR-579 hsa-miR-1273d hsa-miR-409-5p hsa-miR-3649 hsa-miR-4273 hsa-miR-92b hsa-miR-130b
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    Additional mRNA sequence: 

    AF012073.1 AF012074.1 AF536975.1 AF536976.1 AF536977.1 AF536980.1 AJ250852.1 AJ250854.1 
    AJ250855.1 AK307363.1 AY245866.1 AY245867.1 AY388960.1 BC008390.1 BC036319.1 BT007398.1 
    BX641110.1 BX648604.1 L20970.1 U02882.1 U50157.1 U50158.1 U50159.1 U79571.1 

    21 DOTS entries:

    DT.92426903  DT.100679149  DT.86845970  DT.100707106  DT.427208  DT.91711773  DT.92426905  DT.310355 
    DT.101980313  DT.95192816  DT.100786878  DT.452708  DT.101973612  DT.100786875  DT.100786876  DT.121622851 
    DT.40199937  DT.75187142  DT.97824940  DT.99933158  DT.120842770 

    Selected AceView cDNA sequences (see all 148):

    C02601 U79571 CR595345 BU689571 AA862496 AI088266 BM998504 AL700152 
    AA609831 AJ250852 AL043507 CR603521 AJ250854 BF059734 AY388960 AL698930 
    BF222214 AI798641 AY245867 AI745589 CB148117 AA868385 AA371007 CD679318 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for PDE4D (see all 11)    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^
    SP1:                          -     -     -     -           -                       -     -     -           -                                                   
    SP2:                                -     -     -           -                       -     -     -           -                                                   
    SP3:        -     -     -     -     -     -     -           -                       -     -     -           -                                                   
    SP4:                                      -     -           -                       -     -     -           -                                                   
    SP5:                                            -           -                       -     -     -           -                                                   

    ExUns: 24a · 24b · 24c · 24d · 24e · 24f
    SP1:                                    
    SP2:                                    
    SP3:                                    
    SP4:                                    
    SP5:                                    


    ECgene alternative splicing isoforms for PDE4D

    (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)
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    PDE4D expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    PDE4D Expression
    About this image


    PDE4D expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Brain (Nervous System)    fully expand to see all 8 entries
             Cerebral Cortex
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Lung (Respiratory System)    fully expand to see all 2 entries
             Stem Bronchi
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Eye (Sensory Organs)
             Lens
    PDE4D Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    PDE4D Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.117545

    UniProtKB/Swiss-Prot: PDE4D_HUMAN, Q08499
    Tissue specificity: Expressed in colonic epithelial cells (at protein level). Widespread; most abundant in
    skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney.
    Isoform 7 is detected in heart and skeletal muscle

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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)
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    This gene was present in the common ancestor of animals.

    Orthologs for PDE4D gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Pde4d5 phosphodiesterase 4D, cAMP specific   --   13 (59.69 cM) 108449948 
    chicken
    (Gallus gallus)
    Aves PDE4D1 phosphodiesterase 4D, cAMP-specific 84.86(n)
    95.69(a)
      769469  XM_003642985.2  XP_003643033.2 
    lizard
    (Anolis carolinensis)
    Reptilia PDE4D6
    phosphodiesterase 4D, cAMP-specific
    91(a)
    1 ↔ 1
    2(9592183-9852488)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.217052 Xenopus laevis transcribed sequence with moderate similarity more 81.34(n)    BX852466.1 
    zebrafish
    (Danio rerio)
    Actinopterygii pde4d1 phosphodiesterase 4D, cAMP-specific 75.16(n)
    88.57(a)
      566998  XM_690282.5  XP_695374.5 
    fruit fly
    (Drosophila melanogaster)
    Insecta dnc1 , 3 behavior cAMP-specific
    phosphodiesterase3
    dunce1
    61(a)3
    60.14(n)1
    63.02(a)1
      313091  NM_166970.21  NP_726858.21 
    worm
    (Caenorhabditis elegans)
    Secernentea R153.1b3
    pde-41
    pde-41 57(a)
    (best of 2)3
    55.97(n)1
    56.93(a)1
      II(7627989-7649880)3
    1742351  NM_182145.31  NP_871945.11 


    ENSEMBL Gene Tree for PDE4D (if available)
    TreeFam Gene Tree for PDE4D (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for PDE4D gene
    PDE8B2  PDE4B2  PDE4C2  PDE7B2  PDE1B2  PDE1A2  PDE9A2  PDE1C2  
    PDE7A2  PDE8A2  PDE4A2  
    17 SIMAP similar genes for PDE4D using alignment to 6 protein entries:     PDE4D_HUMAN (see all proteins):
    HSPDE4D    PDE4    PDE4B    PDE4C    PDE4A    PDE8B
    PDE8A    DKFZp686L23131    PDE1C    PDE1A    PDE7B    PDE2A
    PDE1B    PDE6B    PDE7A    PDE11A    PDE9A

    Find genes that share paralogs with PDE4D           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 PDE4D (see all 28971)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 5 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0682444
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0682442 F S mis40--------
    VAR_0682434
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0682432 P T mis40--------
    VAR_0694554
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694552 I T mis40--------
    VAR_0694494
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694492 Q E mis40--------
    VAR_0694484
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694482 A S mis40--------
    VAR_0694504
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694502 S T mis40--------
    VAR_0694544
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694542 G D mis40--------
    VAR_0694534
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694532 E A mis40--------
    VAR_0682424
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0682422 S A mis40--------
    VAR_0694514
    Acrodysostosis 2, with or without hormone resistance (ACRDYS2)4--see VAR_0694512 A V mis40--------

    HapMap Linkage Disequilibrium report for PDE4D (58264865 - 58514865 bp, first 250kb of PDE4D)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for PDE4D (see all 63):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2730229CNV Deletion23290073
    esv2730226CNV Deletion23290073
    esv2730230CNV Deletion23290073
    esv2730237CNV Deletion23290073
    esv2660953CNV Deletion23128226
    esv2309169CNV Deletion18987734
    esv2665058CNV Deletion23128226
    esv2672705CNV Deletion23128226
    esv2730225CNV Deletion23290073
    esv2730234CNV Deletion23290073

    Human Gene Mutation Database (HGMD): PDE4D
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing PDE4D
    DNA2.0 Custom Variant and Variant Library Synthesis for PDE4D

    (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.)
    About This Section

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    OMIM gene information: 600129   
    OMIM disorders: 606799  614613  
    UniProtKB/Swiss-Prot: PDE4D_HUMAN, Q08499
  • Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457
    states that association with stroke has to be considered with caution
  • Acrodysostosis 2, with or without hormone resistance (ACRDYS2) [MIM:614613]: A pleiotropic disorder
    characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly,
    midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities
    include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a
    common finding but is variable in severity and can be associated with significant behavioral problems. Note=The
    disease is caused by mutations affecting the gene represented in this entry

  • 3 diseases for PDE4D:    
    About MalaCards
    acrodysostosis 2, with or without hormone resistance    acrodysostosis 1, with or without hormone resistance    acrodysostosis

    2 diseases from the University of Copenhagen DISEASES database for PDE4D:
    Acrodysostosis     Cerebrovascular accident

    Find genes that share disorders with PDE4D           About GenesLikeMe

    9 Novoseek inferred disease relationships for PDE4D gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    stroke 56.9 108 16914755 (7), 18694398 (4), 19399275 (4), 16543535 (4) (see all 29)
    cerebral infarction 11 3 16322495 (3)
    pulmonary disease chronic obstructive 9.66 1 17016624 (1)
    respiratory disease 6.03 1 15576036 (1)
    atherosclerosis 1.89 3 14517540 (2), 15802632 (1)
    asthma 0 3 19426955 (2)
    myocardial infarction 0 3 15861005 (1), 16635437 (1), 16213210 (1)
    infarct 0 2 15861005 (1), 16162858 (1)
    coronary artery disease 0 1 15861005 (1)

    Genetic Association Database (GAD): PDE4D
    Human Genome Epidemiology (HuGE) Navigator: PDE4D (48 documents)

    Export disorders for PDE4D 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 PDE4D gene, integrated from 10 sources (see all 247):
    (articles sorted by number of sources associating them with PDE4D)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. (PubMed id 14517540)1, 2, 4, 9 Gretarsdottir S.... Gulcher J.R. (Nat. Genet. 2003)
    2. Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese population. (PubMed id 19786079)1, 4, 9 Li N....Zhang H. (Brain Res. Bull. 2010)
    3. PDE4D and ALOX5AP genetic variants and risk for Ischemic Cerebrovascular Disease in Sweden. (PubMed id 17655870)1, 4, 9 Kostulas K....Hillert J. (J. Neurol. Sci. 2007)
    4. Genome-wide association analysis identifies PDE4D as an asthma-susceptibility gene. (PubMed id 19426955)1, 4, 9 Himes B.E....Weiss S.T. (Am. J. Hum. Genet. 2009)
    5. Phosphodiesterase 4D and 5-lipoxygenase activating protein genes and risk of ischemic stroke in Sardinians. (PubMed id 19417766)1, 4, 9 Quarta G....Rubattu S. (Eur. J. Hum. Genet. 2009)
    6. Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohort. (PubMed id 16543535)1, 4, 9 KuhlenbAoumer G....Stoll M. (J. Neurol. Neurosurg. Psychiatr. 2006)
    7. ALOX5AP gene and the PDE4D gene in a central European population of stroke patients. (PubMed id 15731479)1, 4, 9 LA/hmussaar E....Dichgans M. ( a journal of cerebral circulation 2005)
    8. Association between the PDE4D gene and ischaemic stroke in the Chinese Han population. (PubMed id 19196240)1, 4, 9 Sun Y....He L. (Clin. Sci. 2009)
    9. Phosphodiesterase 4D gene and risk of noncardiogenic ischemic stroke in a Korean population. (PubMed id 19399275)1, 4, 9 Kim M.K....Cho K.H. (J. Korean Med. Sci. 2009)
    10. Phosphodiesterase 4D gene polymorphism is associated with ischaemic and haemorrhagic stroke. (PubMed id 18694398)1, 4, 9 Xue H....Hui R. (Clin. Sci. 2009)

    (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: 5144 HGNC: 8783 AceView: PDE4D Ensembl:ENSG00000113448 euGenes: HUgn5144
    ECgene: PDE4D Kegg: 5144 H-InvDB: PDE4D

    (According to HUGE)
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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)
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    NameDescription
    PharmGKB entry for PDE4D Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for PDE4D gene:
    Search GeneIP for patents involving PDE4D

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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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     Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PDE4D
     Browse compounds at ApexBio
     Search Addgene for plasmids for PDE4D
      Search eBioscience for proteins for PDE4D
      Search eBioscience for elisas for PDE4D
      eBioscience FlowRNA Probe Sets
     genOway: Develop your customized and physiologically relevant rodent model for PDE4D
     antibodies-online antibodies for PDE4D (69 products)
     antibodies-online kits for PDE4D (23 products)
     antibodies-online peptides for PDE4D
     antibodies-online proteins for PDE4D (6 products)
           
    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014 , 7 Oct 2014

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