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PDE4A phosphodiesterase 4A [ Homo sapiens (human) ]

Gene ID: 5141, updated on 27-Nov-2024

Summary

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Official Symbol
PDE4Aprovided by HGNC
Official Full Name
phosphodiesterase 4Aprovided by HGNC
Primary source
HGNC:HGNC:8780
See related
Ensembl:ENSG00000065989 MIM:600126; AllianceGenome:HGNC:8780
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PDE4; DPDE2; PDE46
Summary
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]
Expression
Ubiquitous expression in testis (RPKM 5.3), brain (RPKM 5.3) and 24 other tissues See more
Orthologs
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Genomic context

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See PDE4A in Genome Data Viewer
Location:
19p13.2
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (10416773..10469631)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (10543231..10596068)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (10527449..10580307)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10463923-10464686 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10474734-10475234 Neighboring gene tyrosine kinase 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:10491214-10491877 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13962 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13963 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10499431-10499931 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10066 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13965 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10067 Neighboring gene cell division cycle 37, HSP90 cochaperone Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13966 Neighboring gene microRNA 1181 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10068 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13967 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10527911-10528462 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10528463-10529013 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10530007-10530886 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10069 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10070 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13969 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10071 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10072 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10542553-10543236 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10543237-10543919 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10546465-10546964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13970 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13971 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10075 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10076 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10572008-10572732 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13973 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:10602595-10603095 Neighboring gene Sharpr-MPRA regulatory region 8442 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13974 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:10612744-10613299 Neighboring gene kelch like ECH associated protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10078 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10625413-10626006 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:10626007-10626600 Neighboring gene sphingosine-1-phosphate receptor 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Helix-1 of the cAMP-specific phosphodiesterase PDE4A1 regulates its phospholipase-D-dependent redistribution in response to release of Ca2+. Huston E, et al. J Cell Sci, 2006 Sep 15. PMID 16940352
  2. Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits. Niccolini F, et al. Neurology, 2017 Aug 8. PMID 28701494
  3. Identification of a multifunctional docking site on the catalytic unit of phosphodiesterase-4 (PDE4) that is utilised by multiple interaction partners. Houslay KF, et al. Biochem J, 2017 Feb 15. PMID 27993970, Free PMC Article
  4. Safety and Pharmacodynamics of the PDE4 Inhibitor Roflumilast in Advanced B-cell Malignancies. Kelly K, et al. Clin Cancer Res, 2017 Mar 1. PMID 27542768, Free PMC Article
  5. Key role of phosphodiesterase 4A (PDE4A) in autophagy triggered by yessotoxin. Fernández-Araujo A, et al. Toxicology, 2015 Mar 2. PMID 25576684

See all (96) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Low PDE4A expression promoted the progression of ovarian cancer by inducing Snail nuclear translocation.
    Title: Low PDE4A expression promoted the progression of ovarian cancer by inducing Snail nuclear translocation.
  2. Regulatory pathways and therapeutic potential of PDE4 in liver pathophysiology.
    Title: Regulatory pathways and therapeutic potential of PDE4 in liver pathophysiology.
  3. PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis.
    Title: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis.
  4. Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.
    Title: Combined PDE4+MEK inhibition shows antiproliferative effects in NRASQ61 mutated melanoma preclinical models.
  5. Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.
    Title: Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.
  6. Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behcet's Disease.
    Title: Reduction of Neutrophil Activation by Phosphodiesterase 4 Blockade in Behçet's Disease.
  7. Phosphodiesterase (PDE) 4 inhibition boosts Schwann cell myelination in a 3D regeneration model.
    Title: Phosphodiesterase (PDE) 4 inhibition boosts Schwann cell myelination in a 3D regeneration model.
  8. Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.
    Title: Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.
  9. Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation.
    Title: Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation.
  10. The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease.
    Title: The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease.
Submit: New GeneRIF Correction See all GeneRIFs (62)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat Cyclic AMP phosphodiesterase inhibitors AV411 and AV1013 inhibit HIV-1 replication and block HIV-1 Tat-induced neurotoxicity in human microglia, suggesting that cyclic AMP phosphodiesterase is involved in the Tat-mediated neurotoxicity PubMed
tat HIV-1 Tat decreases the intracellular levels of cAMP and CREB ser-133 phosphorylation through a signal transduction pathway involving sequential activation of phosphatidylinositol 3-kinase, AKT, and cyclic nucleoside phosphodiesterases PubMed
tat HIV-1 Tat protein, in combination with anti-CD3/CD28 mAbs, promotes IL-2 production and proliferation of primary CD4+ T lymphocytes by recruiting cyclic nucleoside phosphodiesterase 4, resulting in increased susceptibility to HIV-1 infection PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 3',5'-cyclic-AMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables 3',5'-cyclic-AMP phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 3',5'-cyclic-AMP phosphodiesterase activity IGI
Inferred from Genetic Interaction
more info
 PubMed 
enables 3',5'-cyclic-AMP phosphodiesterase activity TAS
Traceable Author Statement
more info
  
enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cAMP binding IGI
Inferred from Genetic Interaction
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
  
involved_in cAMP catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cAMP catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cAMP-mediated signaling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to xenobiotic stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of cAMP/PKA signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in sensory perception of smell IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extrinsic component of membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in ruffle membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
3',5'-cyclic-AMP phosphodiesterase 4A
Names
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
cAMP-specific phosphodiesterase 4A
phosphodiesterase 4A, cAMP-specific (dunce
phosphodiesterase E2 dunce homolog, Drosophila
phosphodiesterase isozyme 4
NP_001104777.1
NP_001104778.1
NP_001104779.1
NP_001230050.1
NP_006193.1
XP_011526357.1
XP_016882354.1
XP_047294866.1
XP_047294867.1
XP_047294868.1
XP_047294869.1
XP_047294870.1
XP_047294871.1
XP_054177156.1
XP_054177157.1
XP_054177158.1
XP_054177159.1
XP_054177160.1
XP_054177161.1
XP_054177162.1
XP_054177163.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029594.1 RefSeqGene

    Range
    8766..57858
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001111307.2 → NP_001104777.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 1

    See identical proteins and their annotated locations for NP_001104777.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC011461, AC011548, BC038234, BE266386, BQ009232, L20965
    Consensus CDS
    CCDS45961.1
    UniProtKB/Swiss-Prot
    O75522, O76092, P27815, Q16255, Q16691, Q5DM53, Q6PMT2, Q8IVA7, Q8WUQ3, Q9H3H2
    Related
    ENSP00000370078.3, ENST00000380702.7
    Conserved Domains (1) summary
    pfam00233
    Location:432 → 673
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  2. NM_001111308.1 → NP_001104778.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 2

    See identical proteins and their annotated locations for NP_001104778.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as PDE4A11) contains an alternative 5' terminal exon compared to variant 1. It encodes a shorter isoform (2) with a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC011461, AW138155, AY593872, AY618547, BC038234, BE266386, BQ009232, L20965
    Consensus CDS
    CCDS45962.1
    UniProtKB/Swiss-Prot
    P27815
    Related
    ENSP00000293683.4, ENST00000293683.9
    Conserved Domains (1) summary
    pfam00233
    Location:406 → 647
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  3. NM_001111309.1 → NP_001104779.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 3

    See identical proteins and their annotated locations for NP_001104779.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as HSPDE4A10) contains an alternative 5' terminal exon compared to variant 1. It encodes a shorter isoform (3) with a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC011461, AF073745, AW138155, BC038234, BE266386, BQ009232, L20965
    Consensus CDS
    CCDS45963.1
    UniProtKB/Swiss-Prot
    P27815
    Related
    ENSP00000394754.1, ENST00000440014.6
    Conserved Domains (1) summary
    pfam00233
    Location:371 → 612
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  4. NM_001243121.2 → NP_001230050.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 5

    See identical proteins and their annotated locations for NP_001230050.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) contains additional exons at the 5' end compared to variant 1. It encodes a shorter isoform (5, also known as PDE4A8) with a distinct N-terminus compared to isoform 1. This isoform is expressed predominantly in skeletal muscle and brain, a pattern that differs from that of other isoforms, and thus may have a specific function in regulating cAMP levels in human skeletal muscle and brain (PMID:18095939).
    Source sequence(s)
    AC011461, AC011548, AW138155, AY593872, S75213
    Consensus CDS
    CCDS58649.1
    UniProtKB/Swiss-Prot
    P27815
    Related
    ENSP00000468507.1, ENST00000592685.5
    Conserved Domains (1) summary
    pfam00233
    Location:410 → 651
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  5. NM_006202.3 → NP_006193.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 4

    See identical proteins and their annotated locations for NP_006193.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternative 5' terminal exon and is missing several 5' coding exons compared to variant 1. It encodes a shorter isoform (4) with a distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AC011461, AC011529, BC038234, BE266386, BQ009232, L20965
    Consensus CDS
    CCDS12238.1
    UniProtKB/Swiss-Prot
    P27815
    Related
    ENSP00000341007.2, ENST00000344979.7
    Conserved Domains (1) summary
    pfam00233
    Location:193 → 434
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    10416773..10469631
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047438910.1 → XP_047294866.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X2

  2. XM_011528055.4 → XP_011526357.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X5

    Conserved Domains (1) summary
    pfam00233
    Location:432 → 643
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

  3. XM_017026865.3 → XP_016882354.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X1

  4. XM_047438913.1 → XP_047294869.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X6

  5. XM_047438911.1 → XP_047294867.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X3

  6. XM_047438914.1 → XP_047294870.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X7

  7. XM_047438912.1 → XP_047294868.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X4

  8. XM_047438915.1 → XP_047294871.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X8

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    10543231..10596068
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321182.1 → XP_054177157.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X2

  2. XM_054321185.1 → XP_054177160.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X5

  3. XM_054321181.1 → XP_054177156.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X1

  4. XM_054321186.1 → XP_054177161.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X6

  5. XM_054321183.1 → XP_054177158.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X3

  6. XM_054321187.1 → XP_054177162.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X7

  7. XM_054321184.1 → XP_054177159.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X4

  8. XM_054321188.1 → XP_054177163.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X8

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P27815.3 GenPept UniProtKB/Swiss-Prot:P27815

Gene LinkOut

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