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    Pde4a phosphodiesterase 4A, cAMP specific [ Mus musculus (house mouse) ]

    Gene ID: 18577, updated on 27-Nov-2024

    Summary

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    Official Symbol
    Pde4aprovided by MGI
    Official Full Name
    phosphodiesterase 4A, cAMP specificprovided by MGI
    Primary source
    MGI:MGI:99558
    See related
    Ensembl:ENSMUSG00000032177 AllianceGenome:MGI:99558
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Dpde2; D9Ertd60e
    Summary
    Enables 3',5'-cyclic-AMP phosphodiesterase activity. Involved in cAMP catabolic process. Acts upstream of or within cellular response to xenobiotic stimulus; regulation of signal transduction; and sensory perception of smell. Located in cytosol and membrane. Is expressed in several structures, including alimentary system; heart; integumental system; nervous system; and sensory organ. Orthologous to human PDE4A (phosphodiesterase 4A). [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Broad expression in testis adult (RPKM 20.4), frontal lobe adult (RPKM 16.0) and 22 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Pde4a in Genome Data Viewer
    Location:
    9 A3; 9 7.73 cM
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 9 NC_000075.7 (21076998..21124544)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 9 NC_000075.6 (21165700..21213248)

    Chromosome 9 - NC_000075.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E5054 Neighboring gene cell division cycle 37 Neighboring gene predicted gene, 36118 Neighboring gene predicted gene, 35977 Neighboring gene CapStarr-seq enhancer MGSCv37_chr9:20966019-20966202 Neighboring gene predicted gene, 39301 Neighboring gene STARR-positive B cell enhancer ABC_E1781 Neighboring gene STARR-seq mESC enhancer starr_23485 Neighboring gene predicted gene, 16754 Neighboring gene STARR-seq mESC enhancer starr_23486 Neighboring gene kelch-like ECH-associated protein 1 Neighboring gene STARR-positive B cell enhancer ABC_E8278 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: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Physical mapping and promoter structure of the murine cAMP-specific phosphodiesterase pde4a gene. Olsen AE, et al. Mamm Genome, 2000 Jan. PMID 10602991
    2. 6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury. Tsai YF, et al. Free Radic Biol Med, 2017 May. PMID 28263828
    3. Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior. Hansen RT 3rd, et al. Psychopharmacology (Berl), 2014 Aug. PMID 24563185
    4. Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins. Tibbo AJ, et al. J Mol Cell Cardiol, 2022 Apr. PMID 34999055, Free PMC Article
    5. Stimulation of p70S6 kinase via a growth hormone-controlled phosphatidylinositol 3-kinase pathway leads to the activation of a PDE4A cyclic AMP-specific phosphodiesterase in 3T3-F442A preadipocytes. MacKenzie SJ, et al. Proc Natl Acad Sci U S A, 1998 Mar 31. PMID 9520403, Free PMC Article

    See all (60) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. In conclusion, our data demonstrated that UFM24 inhibits oxidative burst in human neutrophils through inhibition of PDE4 activity. UFM24 also exhibited significant protection against endotoxin-induced acute lung injury (ALI)in mice. UFM24 has potential as an anti-inflammatory agent for treating neutrophilic lung damage.
      Title: 6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury.
    4. PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.
      Title: PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.
    5. results suggest that PDE4A may be important in the regulation of emotional memory and anxiety-like behavior, but not emesis
      Title: Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.
    6. This study showed that long PDE4 isoforms provide a novel node for cross-talk between the cAMP and p38 MAPK signalling systems at the level of MK2.
      Title: Phosphorylation of cAMP-specific PDE4A5 (phosphodiesterase-4A5) by MK2 (MAPKAPK2) attenuates its activation through protein kinase A phosphorylation.
    7. 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).
    8. a new mechanism in which phosphodiesterase PDE4A4/5 interacts with p75(NTR) to enhance cAMP degradation
      Title: p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    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 MGI

    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 ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables 3',5'-cyclic-AMP phosphodiesterase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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
    		  
    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
    		  
    acts_upstream_of_or_within cellular response to xenobiotic stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in modulation of chemical synaptic transmission ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within regulation of cAMP/PKA signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within sensory perception of smell IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Schaffer collateral - CA1 synapse ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 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
    cAMP-specific 3',5'-cyclic phosphodiesterase 4A
    cAMP-specific phosphodiesterase 4A
    cAMP-specific phosphodiesterase PDE4A
    cyclic AMP specific phosphodiesterase PDE4A5A
    dunce
    NP_001297679.1
    NP_001396218.1
    NP_001396220.1
    NP_001396221.1
    NP_001396222.1
    NP_001396223.1
    NP_001396224.1
    NP_001396225.1
    NP_001396226.1
    NP_062772.3
    NP_899668.1
    XP_030099987.1

    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_001310750.2 → NP_001297679.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 6

      See identical proteins and their annotated locations for NP_001297679.1

      Status: VALIDATED

      Source sequence(s)
      AC163637
      Consensus CDS
      CCDS80964.1
      UniProtKB/TrEMBL
      Q3TUD0
      Related
      ENSMUSP00000111118.3, ENSMUST00000115458.9
      Conserved Domains (1) summary
      pfam00233
      Location:361 → 602
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    2. NM_001409289.1 → NP_001396218.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC163637

    3. NM_001409291.1 → NP_001396220.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC163637
      UniProtKB/TrEMBL
      A0AAQ4VMW1
      Related
      ENSMUSP00000160020.1, ENSMUST00000249923.1

    4. NM_001409292.1 → NP_001396221.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC163637

    5. NM_001409293.1 → NP_001396222.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 8

      Status: VALIDATED

      Source sequence(s)
      AC163637

    6. NM_001409294.1 → NP_001396223.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 8

      Status: VALIDATED

      Source sequence(s)
      AC163637

    7. NM_001409295.1 → NP_001396224.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 9

      Status: VALIDATED

      Source sequence(s)
      AC163637

    8. NM_001409296.1 → NP_001396225.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 10

      Status: VALIDATED

      Source sequence(s)
      AC163637

    9. NM_001409297.1 → NP_001396226.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 10

      Status: VALIDATED

      Source sequence(s)
      AC163637

    10. NM_019798.6 → NP_062772.3  3',5'-cyclic-AMP phosphodiesterase 4A isoform 1

      See identical proteins and their annotated locations for NP_062772.3

      Status: VALIDATED

      Source sequence(s)
      AC163637
      Consensus CDS
      CCDS22896.1
      UniProtKB/TrEMBL
      C9K100
      Related
      ENSMUSP00000003395.10, ENSMUST00000003395.10
      Conserved Domains (1) summary
      pfam00233
      Location:184 → 425
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    11. NM_183408.4 → NP_899668.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform 5

      See identical proteins and their annotated locations for NP_899668.1

      Status: VALIDATED

      Source sequence(s)
      AC163637
      Consensus CDS
      CCDS22895.1
      UniProtKB/Swiss-Prot
      O89084, Q8R078, Q9JHQ4, Q9QX48, Q9QX49, Q9QXI8
      UniProtKB/TrEMBL
      B2RTL2, Q3TUD0
      Related
      ENSMUSP00000037025.9, ENSMUST00000039413.15
      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_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000075.7 Reference GRCm39 C57BL/6J

      Range
      21076998..21124544
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_030244127.1 → XP_030099987.1  3',5'-cyclic-AMP phosphodiesterase 4A isoform X3

      UniProtKB/TrEMBL
      C9K100
      Conserved Domains (1) summary
      pfam00233
      Location:100 → 341
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    RNA

    1. XR_003947813.2 RNA Sequence

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O89084.2 GenPept UniProtKB/Swiss-Prot:O89084

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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