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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
    mouse all
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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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    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

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