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Aliases for PDE4A Gene

Aliases for PDE4A Gene

  • Phosphodiesterase 4A, CAMP-Specific 2 3
  • DPDE2 3 4 6
  • PDE46 3 4
  • Phosphodiesterase 4A, CAMP-Specific (Dunce (Drosophila)-Homolog Phosphodiesterase E2) 2
  • Phosphodiesterase E2 Dunce Homolog (Drosophila) 2
  • Phosphodiesterase E2 Dunce Homolog, Drosophila 3
  • CAMP-Specific 3,5-Cyclic Phosphodiesterase 4A 3
  • Phosphodiesterase 4A, CAMP-Specific (Dunce 3
  • Phosphodiesterase Isozyme 4 3
  • EC 3.1.4.17 63
  • EC 3.1.4.53 4
  • EC 3.1.4 63
  • PDE4 3

External Ids for PDE4A Gene

Previous HGNC Symbols for PDE4A Gene

  • DPDE2

Previous GeneCards Identifiers for PDE4A Gene

  • GC19P010663
  • GC19P010376
  • GC19P010527
  • GC19P010111

Summaries for PDE4A Gene

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 and asthma. Among its related pathways are Signaling by GPCR and Signaling by GPCR. GO annotations related to this gene include cAMP binding and 3,5-cyclic-AMP phosphodiesterase activity. An important paralog of this gene is PDE7A.

UniProtKB/Swiss-Prot for PDE4A Gene

  • Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Tocris 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

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PDE4A Gene

Genomics for PDE4A Gene

Regulatory Elements for PDE4A Gene

Genomic Location for PDE4A Gene

Start:
10,416,773 bp from pter
End:
10,469,631 bp from pter
Size:
52,859 bases
Orientation:
Plus strand

Genomic View for PDE4A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PDE4A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDE4A Gene

Proteins for PDE4A Gene

  • Protein details for PDE4A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P27815-PDE4A_HUMAN
    Recommended name:
    cAMP-specific 3,5-cyclic phosphodiesterase 4A
    Protein Accession:
    P27815
    Secondary Accessions:
    • O75522
    • O76092
    • Q16255
    • Q16691
    • Q5DM53
    • Q6PMT2
    • Q8IVA7
    • Q8WUQ3
    • Q9H3H2

    Protein attributes for PDE4A Gene

    Size:
    886 amino acids
    Molecular mass:
    98143 Da
    Cofactor:
    Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Note=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.;
    Quaternary structure:
    • Isoform 1 interacts with LYN. Isoform 2 and isoform 6 interact weakly with LYN. Isoform 1, isoform 2 and isoform 6 interact with ARRB2.

    Three dimensional structures from OCA and Proteopedia for PDE4A Gene

    Alternative splice isoforms for PDE4A Gene

neXtProt entry for PDE4A Gene

Proteomics data for PDE4A Gene at MOPED

Post-translational modifications for PDE4A Gene

  • 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 PKA.
  • Proteolytically cleaved by caspase-3
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains for PDE4A Gene

Gene Families for PDE4A Gene

HGNC:
  • PDE :Phosphodiesterases
IUPHAR :

Protein Domains for PDE4A Gene

Suggested Antigen Peptide Sequences for PDE4A Gene

Graphical View of Domain Structure for InterPro Entry

P27815

UniProtKB/Swiss-Prot:

PDE4A_HUMAN :
  • P27815
Family:
  • Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
genes like me logo Genes that share domains with PDE4A: view

Function for PDE4A Gene

Molecular function for PDE4A Gene

GENATLAS Biochemistry: cAMP specific nucleotide phosphodiesterase class IV,A,with homology to Drosophila dunce gene,involved in signal transduction
UniProtKB/Swiss-Prot BiophysicochemicalProperties: Kinetic parameters: KM=4.0 uM for cAMP (isoform 2) {ECO:0000269 PubMed:11306681, ECO:0000269 PubMed:15738310}; KM=3 uM for cAMP (isoform 6) {ECO:0000269 PubMed:11306681, ECO:0000269 PubMed:15738310};
UniProtKB/Swiss-Prot CatalyticActivity: Adenosine 3,5-cyclic phosphate + H(2)O = adenosine 5-phosphate
UniProtKB/Swiss-Prot EnzymeRegulation: 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.
UniProtKB/Swiss-Prot Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Enzyme Numbers (IUBMB) for PDE4A Gene

Gene Ontology (GO) - Molecular Function for PDE4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004114 3,5-cyclic-nucleotide phosphodiesterase activity --
GO:0004115 3,5-cyclic-AMP phosphodiesterase activity IGI 8413254
GO:0005515 protein binding IPI 11306681
GO:0030552 cAMP binding IGI 8413254
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with PDE4A: view
genes like me logo Genes that share phenotypes with PDE4A: view

Animal Models for PDE4A Gene

MGI Knock Outs for PDE4A:

miRNA for PDE4A Gene

miRTarBase miRNAs that target PDE4A

No data available for Transcription Factor Targeting and HOMER Transcription for PDE4A Gene

Localization for PDE4A Gene

Subcellular locations from UniProtKB/Swiss-Prot for PDE4A Gene

Isoform 1: Cytoplasm, perinuclear region.
Isoform 2: Cytoplasm, perinuclear region. Cell projection, ruffle membrane.
Isoform 4: Membrane; Peripheral membrane protein. Note=Isoform 4 has propensity for association with membranes.
Isoform 6: Cytoplasm, perinuclear region.
Isoform 7: Cytoplasm. Membrane. Note=Predominantly cytoplasmic.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PDE4A Gene COMPARTMENTS Subcellular localization image for PDE4A gene
Compartment Confidence
plasma membrane 5
cytosol 4
extracellular 2
nucleus 2
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for PDE4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane --
GO:0016020 membrane TAS 9677330
GO:0032587 ruffle membrane IEA --
genes like me logo Genes that share ontologies with PDE4A: view

Pathways for PDE4A Gene

genes like me logo Genes that share pathways with PDE4A: view

Pathways by source for PDE4A Gene

UniProtKB/Swiss-Prot P27815-PDE4A_HUMAN

  • Pathway: Purine metabolism; 3,5-cyclic AMP degradation; AMP from 3,5-cyclic AMP: step 1/1

Interacting Proteins for PDE4A Gene

Selected Interacting proteins: P27815-PDE4A_HUMAN for PDE4A Gene via MINT I2D

Gene Ontology (GO) - Biological Process for PDE4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006198 cAMP catabolic process IMP 17704206
GO:0007165 signal transduction IEA --
GO:0007608 sensory perception of smell IEA --
GO:0008152 metabolic process --
GO:0010738 regulation of protein kinase A signaling IEA --
genes like me logo Genes that share ontologies with PDE4A: view

Compounds for PDE4A Gene

(5) Tocris Compounds for PDE4A Gene

Compound Action Cas Number
(R)-(-)-Rolipram PDE4 inhibitor. More active enantiomer of rolipram (Cat. No. 0905) [85416-75-7]
Cilostamide PDE3 inhibitor [68550-75-4]
IBMX PDE inhibitor (non-selective) [28822-58-4]
Rolipram PDE4 inhibitor [61413-54-5]
Sildenafil citrate Orally active, potent PDE5 inhibitor [171599-83-0]

(6) HMDB Compounds for PDE4A Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Cyclic AMP
  • Cyclic AMP
60-92-4
Cyclic GMP
  • 3',5'-cyclic GMP
7665-99-8
Guanosine monophosphate
  • 5'-GMP
85-32-5
Theophylline
  • 1,3-Dimethylxanthine
58-55-9

(15) Drugbank Compounds for PDE4A Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
(4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one
target
4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid
target
Dipyridamole
  • Dipiridamol
58-32-2 target inhibitor
Drotaverine
985-12-6 target inhibitor
Dyphylline
  • Dihydroxypropyl Theophylline
479-18-5 target inhibitor

(3) IUPHAR Ligand for PDE4A Gene

Ligand Type Action Affinity Pubmed IDs
YM976 Inhibitor Inhibition 8.3
rolipram Inhibitor Inhibition 7.2
Ro201724 Inhibitor Inhibition 6.2

(124) Novoseek inferred chemical compound relationships for PDE4A Gene

Compound -log(P) Hits PubMed IDs
rolipram 96.8 154
roflumilast 96.1 86
cilomilast 95.7 58
piclamilast 92.3 17
cdp 840 90.2 8
genes like me logo Genes that share compounds with PDE4A: view

Transcripts for PDE4A Gene

Unigene Clusters for PDE4A Gene

Phosphodiesterase 4A, cAMP-specific:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for PDE4A Gene

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: - - -
SP6: -
SP7: - - - - -
SP8: - - - - -
SP9: -
SP10: -

ExUns: 19b · 19c · 19d
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:

Relevant External Links for PDE4A Gene

GeneLoc Exon Structure for
PDE4A
ECgene alternative splicing isoforms for
PDE4A

Expression for PDE4A Gene

mRNA expression in normal human tissues for PDE4A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, MOPED, and MaxQB for PDE4A Gene

SOURCE GeneReport for Unigene cluster for PDE4A Gene Hs.89901

mRNA Expression by UniProt/SwissProt for PDE4A Gene

P27815-PDE4A_HUMAN
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).
genes like me logo Genes that share expressions with PDE4A: view

No data available for mRNA differential expression in normal tissues for PDE4A Gene

Orthologs for PDE4A Gene

This gene was present in the common ancestor of animals.

Orthologs for PDE4A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PDE4A 36
  • 82 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PDE4A 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PDE4A 35
  • 87.05 (n)
  • 88.74 (a)
PDE4A 36
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Pde4a 35
  • 82.05 (n)
  • 84.82 (a)
Pde4a 16
Pde4a 36
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia PDE4A 36
  • 72 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Pde4a 35
  • 82.92 (n)
  • 85.58 (a)
lizard
(Anolis carolinensis)
Reptilia PDE4A 36
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100488846 35
  • 75.72 (n)
  • 85.99 (a)
zebrafish
(Danio rerio)
Actinopterygii pde4a 35
  • 75.56 (n)
  • 82.58 (a)
pde4a 36
  • 69 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta dnc 37
  • 60 (a)
worm
(Caenorhabditis elegans)
Secernentea R153.1a 37
  • 54 (a)
Species with no ortholog for PDE4A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PDE4A Gene

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

Paralogs for PDE4A Gene

Paralogs for PDE4A Gene

Selected SIMAP similar genes for PDE4A Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with PDE4A: view

Variants for PDE4A Gene

Sequence variations from dbSNP and Humsavar for PDE4A Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type MAF
rs477174 -- 10,433,356(-) ATACA(A/G)TGTCC intron-variant
rs513663 -- 10,428,861(-) GCCAC(C/T)GCGCC intron-variant, upstream-variant-2KB
rs633260 -- 10,430,714(-) TTCCG(C/G)GTTCG intron-variant, upstream-variant-2KB
rs753859 -- 10,420,548(-) GTGCC(C/G)GGCGG upstream-variant-2KB, intron-variant
rs892223 -- 10,420,656(-) GGCCG(C/G)GGTAG upstream-variant-2KB, intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PDE4A Gene

Variant ID Type Subtype PubMed ID
dgv3725n71 CNV Loss 21882294
nsv518008 CNV Gain 19592680
nsv911041 CNV Loss 21882294
nsv521918 CNV Gain 19592680
nsv833744 CNV Loss 17160897

Relevant External Links for PDE4A Gene

HapMap Linkage Disequilibrium report
PDE4A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PDE4A Gene

Disorders for PDE4A Gene

MalaCards: The human disease database

MalaCards: The human disease database. (2) Diseases for PDE4A Gene including...

Search for PDE4A Gene in MalaCards »

(2) University of Copenhagen DISEASES for PDE4A Gene

(62) Novoseek inferred disease relationships for PDE4A Gene

Disease -log(P) Hits PubMed IDs
pulmonary disease chronic obstructive 76.4 62
chronic obstructive asthma 65.6 7
asthma 63.6 83
inflammation 48.7 34
airways disease 46.6 2

Relevant External Links for PDE4A

Genetic Association Database (GAD)
PDE4A
Human Genome Epidemiology (HuGE) Navigator
PDE4A
genes like me logo Genes that share disorders with PDE4A: view

No data available for UniProtKB/Swiss-Prot for PDE4A Gene

Publications for PDE4A Gene

  1. Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change. (PMID: 18095939) Mackenzie K.F. … Bolger G.B. (Biochem. J. 2008) 3 4 23
  2. Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. (PMID: 17727341) Wang H. … Ke H. (Biochem. J. 2007) 4 23
  3. BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells. (PMID: 19642024) Schmidt A.L. … Roesler R. (J. Mol. Neurosci. 2010) 3 23
  4. Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: the role of phosphodiesterase 4. (PMID: 19759179) Kolosionek E. … Pullamsetti S.S. (Mol. Biol. Cell 2009) 3 23
  5. Cytokine-dependent balance of mitogenic effects in primary human lung fibroblasts related to cyclic AMP signaling and phosphodiesterase 4 inhibition. (PMID: 20082309) Selige J. … Dunkern T. (J. Cell. Physiol. 2010) 3 23

Products for PDE4A Gene

Sources for PDE4A Gene

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