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    Pde4a phosphodiesterase 4A [ Rattus norvegicus (Norway rat) ]

    Gene ID: 25638, updated on 27-Dec-2024

    Summary

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    Official Symbol
    Pde4aprovided by RGD
    Official Full Name
    phosphodiesterase 4Aprovided by RGD
    Primary source
    RGD:3279
    See related
    EnsemblRapid:ENSRNOG00000020828 AllianceGenome:RGD:3279
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Rattus norvegicus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
    Also known as
    DPDE2; PHOSA
    Summary
    Enables 3',5'-cyclic-AMP phosphodiesterase activity and TPR domain binding activity. Involved in cAMP catabolic process; modulation of chemical synaptic transmission; and response to xenobiotic stimulus. Located in cytosol and perinuclear region of cytoplasm. Is active in Schaffer collateral - CA1 synapse. Biomarker of brucellosis and visual epilepsy. Orthologous to human PDE4A (phosphodiesterase 4A). [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Biased expression in Muscle (RPKM 72.2), Heart (RPKM 63.3) and 9 other tissues See more
    Orthologs
    human mouse all
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    Genomic context

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    See Pde4a in Genome Data Viewer
    Location:
    8q13
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCr8 (GCF_036323735.1) 8 NC_086026.1 (27966978..28029721)
    RS_2023_06 previous assembly mRatBN7.2 (GCF_015227675.2) 8 NC_051343.1 (19690816..19753538)
    106 previous assembly Rnor_6.0 (GCF_000001895.5) 8 NC_005107.4 (22189533..22234036)

    Chromosome 8 - NC_086026.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC108351660 Neighboring gene cell division cycle 37, HSP90 cochaperone Neighboring gene uncharacterized LOC134480144 Neighboring gene Kelch-like ECH-associated protein 1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
    • Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
    • BioProject: PRJNA238328
    • Publication: PMID 24510058
    • Analysis date: Mon Jun 6 17:44:12 2016

    Bibliography

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    Related articles in PubMed

    1. In vitro inhibition of phosphodiesterase type 4 enhances rat corpus cavernosum nerve-mediated relaxation induced by gasotransmitters. Fernandes VS, et al. Life Sci, 2022 May 1. PMID 35219697
    2. Cloning and characterization of mammalian homologs of the Drosophila dunce+ gene. Davis RL, et al. Proc Natl Acad Sci U S A, 1989 May. PMID 2542942, Free PMC Article
    3. Alternative splicing of cAMP-specific phosphodiesterase mRNA transcripts. Characterization of a novel tissue-specific isoform, RNPDE4A8. Bolger GB, et al. J Biol Chem, 1996 Jan 12. PMID 8557632
    4. Determination of the structure of the N-terminal splice region of the cyclic AMP-specific phosphodiesterase RD1 (RNPDE4A1) by 1H NMR and identification of the membrane association domain using chimeric constructs. Smith KJ, et al. J Biol Chem, 1996 Jul 12. PMID 8663181
    5. Differential expression and regulation of the cAMP-selective phosphodiesterase type 4A splice variants in rat brain by chronic antidepressant administration. D'Sa C, et al. Eur J Neurosci, 2005 Sep. PMID 16190900

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. In vitro inhibition of phosphodiesterase type 4 enhances rat corpus cavernosum nerve-mediated relaxation induced by gasotransmitters.
      Title: In vitro inhibition of phosphodiesterase type 4 enhances rat corpus cavernosum nerve-mediated relaxation induced by gasotransmitters.
    3. Selective changes in cytosolic beta-adrenergic cAMP signals and L-type Calcium Channel regulation by Phosphodiesterases during cardiac hypertrophy.
      Title: Selective changes in cytosolic β-adrenergic cAMP signals and L-type Calcium Channel regulation by Phosphodiesterases during cardiac hypertrophy.
    4. ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion.
      Title: ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion.
    5. PDE4A upregulation during cholestatic liver injury plays a role in inflammation and fibrosis.
      Title: Rolipram attenuates bile duct ligation-induced liver injury in rats: a potential pathogenic role of PDE4.
    6. beta-adrenergic cAMP signals are predominantly regulated by phosphodiesterase type 4 in cultured adult rat aortic smooth muscle cells.
      Title: β-Adrenergic cAMP signals are predominantly regulated by phosphodiesterase type 4 in cultured adult rat aortic smooth muscle cells.
    7. These results indicate that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese population.
      Title: Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with schizophrenia.
    8. Increased cAMP may remodel cAMP-mediated signalling events by not only increasing the expression of specific PDE4 cAMP phosphodiesterases but also by down-regulating specific isoforms, such as is shown here for PDE4A10 in cardiac myocytes.
      Title: In cardiac myocytes, cAMP elevation triggers the down-regulation of transcripts and promoter activity for cyclic AMP phosphodiesterase-4A10 (PDE4A10).
    9. cGMP and cAMP phosphodiesterase PDE4 and AMPK/NOX2 have a role in early cardiac hypertrophy induced by angiotensin II
      Title: Concerted regulation of cGMP and cAMP phosphodiesterases in early cardiac hypertrophy induced by angiotensin II.
    10. unique tissue distribution of PDE4A8, combined with the evolutionary divergence of its N-terminus, suggest that this isoform may have a specific function in regulating cAMP levels in human skeletal muscle and brain
      Title: Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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 RGD

    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 IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables 3',5'-cyclic-AMP phosphodiesterase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3',5'-cyclic-nucleotide phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables TPR domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables cAMP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cAMP binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    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 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 catabolic process ISO
    Inferred from Sequence Orthology
    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
    		  
    acts_upstream_of_or_within cellular response to xenobiotic stimulus ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in modulation of chemical synaptic transmission IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in modulation of chemical synaptic transmission IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of cAMP/PKA signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within regulation of cAMP/PKA signal transduction ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in response to xenobiotic stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in sensory perception of smell IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within sensory perception of smell ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Schaffer collateral - CA1 synapse IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in Schaffer collateral - CA1 synapse IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in extrinsic component of membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    3',5'-cyclic-AMP phosphodiesterase 4A
    Names
    PDE4A10 cAMP phosphodiesterase
    cAMP-specific 3',5'-cyclic phosphodiesterase 4A
    cAMP-specific phosphodiesterase 4A
    phosphodiesterase 4A, cAMP specific
    phosphodiesterase 4A, cAMP-specific (phosphodiesterase E2 dunce homolog, Drosophila)
    NP_001380664.1
    NP_001380665.1
    NP_001380666.1
    NP_037233.4
    XP_063121035.1
    XP_063121036.1
    XP_063121037.1
    XP_063121038.1
    XP_063121039.1
    XP_063121040.1
    XP_063121041.1
    XP_063121042.1
    XP_063121043.1
    XP_063121044.1
    XP_063121045.1

    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.

    mRNA and Protein(s)

    1. NM_001393735.1 → NP_001380664.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 2

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000008
      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A6JNQ0
      Related
      ENSRNOP00000085157.2, ENSRNOT00000109272.2
      Conserved Domains (2) summary
      pfam00233
      Location:361 → 602
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam18100
      Location:116 → 231
      PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)

    2. NM_001393736.1 → NP_001380665.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 3

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000008
      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I5ZV79, A6JNP8
      Related
      ENSRNOP00000082776.1, ENSRNOT00000096283.2
      Conserved Domains (2) summary
      pfam00233
      Location:337 → 578
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam18100
      Location:92 → 207
      PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)

    3. NM_001393737.1 → NP_001380666.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 4

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000008
      UniProtKB/TrEMBL
      A0A8I5ZUU0, A0A8I6GFN4
      Related
      ENSRNOP00000082374.1, ENSRNOT00000112455.2
      Conserved Domains (2) summary
      pfam00233
      Location:184 → 425
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam18100
      Location:22 → 54
      PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)

    4. NM_013101.4 → NP_037233.4  3',5'-cyclic-AMP phosphodiesterase 4A isoform 1

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000008
      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A6JNP9, F1M8I9
      Related
      ENSRNOP00000057815.5, ENSRNOT00000061100.7
      Conserved Domains (2) summary
      pfam00233
      Location:418 → 659
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam18100
      Location:173 → 288
      PDE4_UCR; Phosphodiesterase 4 upstream conserved regions (UCR)

    RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

    Reference GRCr8

    Genomic

    1. NC_086026.1 Reference GRCr8

      Range
      27966978..28029721
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_063264966.1 → XP_063121036.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X2

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7

    2. XM_063264971.1 → XP_063121041.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X4

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I5ZV79, A6JNP8

    3. XM_063264967.1 → XP_063121037.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X2

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7

    4. XM_063264972.1 → XP_063121042.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X4

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I5ZV79, A6JNP8

    5. XM_063264970.1 → XP_063121040.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X3

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I5ZZJ4

    6. XM_063264975.1 → XP_063121045.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X7

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7

    7. XM_063264965.1 → XP_063121035.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X1

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I6ALZ5
      Related
      ENSRNOP00000089924.2, ENSRNOT00000115099.2

    8. XM_063264969.1 → XP_063121039.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X3

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I5ZZJ4

    9. XM_063264968.1 → XP_063121038.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X3

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7
      UniProtKB/TrEMBL
      A0A8I5ZZJ4

    10. XM_063264973.1 → XP_063121043.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X5

      UniProtKB/Swiss-Prot
      P14645, P54748, Q9EQR7

    11. XM_063264974.1 → XP_063121044.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X6

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P54748.1 GenPept UniProtKB/Swiss-Prot:P54748

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