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Aliases for PDE4A Gene

Aliases for PDE4A Gene

  • Phosphodiesterase 4A 2 3 5
  • DPDE2 3 4
  • 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
  • Phosphodiesterase 4A, CAMP-Specific (Dunce 3
  • Phosphodiesterase 4A, CAMP-Specific 2
  • Phosphodiesterase Isozyme 4 3
  • EC 63
  • EC 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) is a Protein Coding gene. Diseases associated with PDE4A include Asthma and Pulmonary Hypertension. Among its related pathways are cAMP signaling pathway and DAG and IP3 signaling. GO annotations related to this gene include 3,5-cyclic-nucleotide phosphodiesterase activity 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 phosphohydrolyases that catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). PDEs regulate the second messengers by controlling their degradation.

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

Enhancers for PDE4A Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around PDE4A on UCSC Golden Path with GeneCards custom track

Promoters for PDE4A Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around PDE4A on UCSC Golden Path with GeneCards custom track

Genomic Location for PDE4A Gene

10,416,773 bp from pter
10,469,631 bp from pter
52,859 bases
Plus strand

Genomic View for PDE4A Gene

Genes around PDE4A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PDE4A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    Recommended name:
    cAMP-specific 3,5-cyclic phosphodiesterase 4A
    Protein Accession:
    Secondary Accessions:
    • O75522
    • O76092
    • Q16255
    • Q16691
    • Q5DM53
    • Q6PMT2
    • Q8IVA7
    • Q8WUQ3
    • Q9H3H2

    Protein attributes for PDE4A Gene

    886 amino acids
    Molecular mass:
    98143 Da
    Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
    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 & Families for PDE4A Gene

Gene Families for PDE4A Gene

Protein Domains for PDE4A Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
  • 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:0005515 protein binding IPI 11306681
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:

Animal Model Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets 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

Jensen Localization Image for PDE4A Gene COMPARTMENTS Subcellular localization image for PDE4A gene
Compartment Confidence
cytosol 5
plasma membrane 5
nucleus 3
cytoskeleton 2
endoplasmic reticulum 2
extracellular 2
mitochondrion 2
lysosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for PDE4A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0016020 membrane TAS 9677330
GO:0048471 perinuclear region of cytoplasm IDA 11306681
genes like me logo Genes that share ontologies with PDE4A: view

Pathways & Interactions 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:0007165 signal transduction IEA --
GO:0008152 metabolic process IEA --
GO:0035690 cellular response to drug IEA --
genes like me logo Genes that share ontologies with PDE4A: view

No data available for SIGNOR curated interactions for PDE4A Gene

Drugs & Compounds for PDE4A Gene

(107) Drugs for PDE4A Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dipyridamole Approved Pharma Inhibition, Inhibitor, inhibitor, Target Adenosine transport inhibitor 78
Dyphylline Approved Pharma inhibitor, Target 0
Roflumilast Approved Pharma inhibitor, Target PDE-4 inhibitor 0
Ibudilast Approved, Investigational Pharma inhibitor, Target 11
Pentoxifylline Approved, Investigational Pharma antibody, Target, inhibitor 92

(60) Additional Compounds for PDE4A Gene - From: Novoseek, HMDB, IUPHAR, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Inhibition, Inhibitor
  • Dihydrogen oxide
  • Steam
Etazolate hydrochloride

(5) Tocris Compounds for PDE4A Gene

Compound Action Cas Number
Dipyridamole Adenosine transport inhibitor 58-32-2
Etazolate hydrochloride PDE4 inhibitor 35838-58-5
MMPX PDE1 inhibitor 78033-08-6
MY-5445 PDE5 inhibitor 78351-75-4
Ro 20-1724 PDE4 inhibitor 29925-17-5

(14) ApexBio Compounds for PDE4A Gene

Compound Action Cas Number
Aminophylline 317-34-0
Anagrelide HCl Thrombocytopenic agent 58579-51-4
Apremilast (CC-10004) PDE4 inhibitor 608141-41-9
Cilomilast Potent PDE4 inhibitor 153259-65-5
Deltarasin KRAS-PDEδ interaction inhibitor 1440898-61-2
Dipyridamole 58-32-2
Doxofylline 69975-86-6
Dyphylline 479-18-5
GSK256066 PDE4-inhibitor,selective and highly potent 801312-28-7
Irsogladine PDE4 inhibitor 57381-26-7
Roflumilast PDE-4 inhibitor 162401-32-3
Rolipram PDE4-inhibitor and an anti-inflammatory agent 61413-54-5
S- (+)-Rolipram CAMP-specific PDE4 inhibitor 85416-73-5
Vinpocetine PDE inhibitor 42971-09-5
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

Relevant External Links for PDE4A Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for PDE4A Gene

mRNA expression in normal human tissues for PDE4A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PDE4A Gene

This gene is overexpressed in Pancreatic juice (54.0) and Frontal cortex (15.0).

Integrated Proteomics: protein expression in normal tissues and cell lines 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

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 expression patterns with PDE4A: view

Protein tissue co-expression partners for PDE4A Gene

Primer Products

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
(Canis familiaris)
Mammalia PDE4A 35
  • 87.05 (n)
  • 88.74 (a)
PDE4A 36
  • 89 (a)
(Mus musculus)
Mammalia Pde4a 35
  • 82.05 (n)
  • 84.82 (a)
Pde4a 16
Pde4a 36
  • 85 (a)
(Rattus norvegicus)
Mammalia Pde4a 35
  • 82.92 (n)
  • 85.58 (a)
(Bos Taurus)
Mammalia PDE4A 36
  • 87 (a)
(Monodelphis domestica)
Mammalia PDE4A 36
  • 72 (a)
(Pan troglodytes)
Mammalia PDE4A 36
  • 82 (a)
(Anolis carolinensis)
Reptilia PDE4A 36
  • 75 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100488846 35
  • 75.72 (n)
  • 85.99 (a)
(Danio rerio)
Actinopterygii pde4a 35
  • 75.56 (n)
  • 82.58 (a)
pde4a 36
  • 69 (a)
fruit fly
(Drosophila melanogaster)
Insecta dnc 37
  • 60 (a)
(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

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

Paralogs for PDE4A Gene

Paralogs for PDE4A Gene

(6) 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
rs1051738 - 10,467,167(+) GACTG(A/C/T)GCAGG reference, missense, utr-variant-3-prime
rs2230190 - 10,467,382(+) TAAGC(C/T)ACAGC downstream-variant-500B, reference, missense
rs7256672 -- 10,468,798(+) TTGCC(G/T)AGCCT utr-variant-3-prime
rs7258359 -- 10,440,205(+) gtctc(A/T)aactc intron-variant
rs7258437 -- 10,440,228(+) gattc(A/T)cccac 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

Variation tolerance for PDE4A Gene

Residual Variation Intolerance Score: 10% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.03; 75.06% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for PDE4A Gene

Disorders for PDE4A Gene

MalaCards: The human disease database

(19) MalaCards diseases for PDE4A Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
  • asthma, protection against
pulmonary hypertension
  • primary pulmonary hypertension
respiratory failure
  • acute and chronic respiratory failure
  • runny nose
chronic lymphocytic leukemia
  • cll
- elite association - COSMIC cancer census association via MalaCards
Search PDE4A in MalaCards View complete list of genes associated with diseases

Relevant External Links for PDE4A

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with PDE4A: view

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

Publications for PDE4A Gene

  1. Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK. (PMID: 20196770) Li X. … Baillie G.S. (Biochem. J. 2010) 3 4 67
  2. Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats. (PMID: 20124930) Yagi K. … Nagahiro S. (Neurosurgery 2010) 23 25 26
  3. Preferential inhibition of human phosphodiesterase 4 by ibudilast. (PMID: 16313925) Huang Z. … Noguchi K. (Life Sci. 2006) 23 25 26
  4. Inhibition of human phosphodiesterase 4A expressed in yeast cell GL62 by theophylline, rolipram, and acetamide-45. (PMID: 12421478) Wang K. … Chen J.C. (Acta Pharmacol. Sin. 2002) 23 25 26
  5. Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP-independent relaxation of the intracranial vertebrobasilar artery. (PMID: 21036126) Yamazaki T. … Matsuzawa S. (Eur. J. Pharmacol. 2011) 25 26

Products for PDE4A Gene

Sources for PDE4A Gene