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    PDE4B phosphodiesterase 4B, cAMP-specific [ Homo sapiens ]

    Gene ID: 5142, updated on 19-May-2012
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    Summary

    Official Symbol
    PDE4Bprovided by HGNC
    Official Full Name
    phosphodiesterase 4B, cAMP-specificprovided by HGNC
    Primary source
    HGNC:8781
    Locus tag
    RP5-876C12.1
    See related
    Ensembl:ENSG00000184588; HPRD:02528; MIM:600127; Vega:OTTHUMG00000009088
    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
    DPDE4; PDE4B5; PDEIVB; MGC126529; DKFZp686F2182
    Summary
    This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    1p31
    Sequence :
    Chromosome: 1; NC_000001.10 (66258193..66840262)
    See PDE4B in Epigenomics, MapViewer

    Chromosome 1 - NC_000001.10Genomic Context describing neighboring genes Neighboring gene leptin receptor overlapping transcript Neighboring gene leptin receptor Neighboring gene UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 11 (GalNAc-T11) pseudogene Neighboring gene SH3-domain GRB2-like (endophilin) interacting protein 1 Neighboring gene microRNA 3117 Neighboring gene Tctex1 domain containing 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    2. Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of select mediators of inflammation in human monocytic cells. Sandeep Varma R, et al. J Immunotoxicol, 2011 Oct-Dec. PMID 21854221.
    3. Gene set enrichment analysis unveils the mechanism for the phosphodiesterase 4B control of glucocorticoid response in B-cell lymphoma. Kim SW, et al. Clin Cancer Res, 2011 Nov 1. PMID 21742807.
    4. Insight into the phosphodiesterase mechanism from combined QM/MM free energy simulations. Wong KY, et al. FEBS J, 2011 Jul. PMID 21595828.
    5. The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion. Selige J, et al. J Cell Physiol, 2011 Aug. PMID 21520048.

    See all (52) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. The reported anti-inflammatory activity of bresol might be attributed to its abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes.
      Title: Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of select mediators of inflammation in human monocytic cells.
    2. Overexpression of the PDE4B in diffuse large B-cell lymphoma (DLBCL) impinge on the same genes/pathways that are abnormally active in GC-resistant tumors.
      Title: Gene set enrichment analysis unveils the mechanism for the phosphodiesterase 4B control of glucocorticoid response in B-cell lymphoma.
    3. found a significant association between PDE4B and PD in the haplotype analysis. Sex-specific analyses demonstrated that PDE4B was associated with PD in females. results suggest PDE4B may play a role in the pathophysiology of PD in the Japanese population.
      Title: Association study of PDE4B with panic disorder in the Japanese population.
    4. Molecular dynamic simulations (with data from crystal structure of catalytic domain of PDE4B with cAMP bound) are used to investigate the catalytic mechanism of PDE4B in the hydrolysis of cAMP.
      Title: Insight into the phosphodiesterase mechanism from combined QM/MM free energy simulations.
    5. these data allow the assignment of different PDE4 subtypes to distinct functions of human lung fibroblasts and highlight the predominant role of PDE4B in controlling pathophysiological processes of human lung fibroblasts.
      Title: The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion.
    6. results do not support a genetic association between tardive dyskinesia and PDE4B
      Title: Phosphodiesterase 4B genetic variants are not associated with antipsychotic-induced tardive dyskinesia.
    7. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Human variation in alcohol response is influenced by variation in neuronal signaling genes.
    10. phosphodiesterase 4B2 gene is an effector of Toll-like receptor signaling in astrocytes, and that its up-regulation at the protein level is controlled by complex mechanisms
      Title: Phosphodiesterase 4B2 gene is an effector of Toll-like receptor signaling in astrocytes.
    Submit: New GeneRIF Correction See all (28)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study.

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Tat 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 Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q07343 P17612 PRKACA    HPRD  PubMed  
    BioGRID:111168 BioGRID:118061 DISC1    BioGRID  PubMed Two-hybrid 
    BioGRID:111168 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • DARPP-32 events, organism-specific biosystem (from REACTOME)
      DARPP-32 events, organism-specific biosystemDopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32), was identified as a major target for dopamine and protein kinase A (PKA) in striatum. Recent advances now indicate that regulation D...
    • G Protein Signaling Pathways, organism-specific biosystem (from WikiPathways)
      G Protein Signaling Pathways, organism-specific biosystemG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades. G proteins are so called because they function as "molecular switches". They...
    • G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • Morphine addiction, organism-specific biosystem (from KEGG)
      Morphine addiction, organism-specific biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
    • Morphine addiction, conserved biosystem (from KEGG)
      Morphine addiction, conserved biosystemMorphine is an alkaloid from the plant extracts of opium poppy. Although morphine is highly effective for the treatment of pain, it is also known to be intensely addictive. We now know that the most ...
    • Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
      Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
    • Opioid Signalling, organism-specific biosystem (from REACTOME)
      Opioid Signalling, organism-specific biosystemOpioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as...
    • Purine metabolism, organism-specific biosystem (from KEGG)
      Purine metabolism, organism-specific biosystem
      Purine metabolism
    • Purine metabolism, conserved biosystem (from KEGG)
      Purine metabolism, conserved biosystem
      Purine metabolism
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    3',5'-cyclic-AMP phosphodiesterase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    phosphoric diester hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    cAMP catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    insoluble fraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    soluble fraction IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    cAMP-specific 3',5'-cyclic phosphodiesterase 4B
    Names
    cAMP-specific 3',5'-cyclic phosphodiesterase 4B
    PDE32
    dunce-like phosphodiesterase E4
    cAMP-specific phosphodiesterase-4 B isoform
    phosphodiesterase 4B, cAMP-specific (phosphodiesterase E4 dunce homolog, Drosophila)
    NP_001032416.1
    NP_001032417.1
    NP_001032418.1
    NP_002591.2
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    NCBI Reference Sequences (RefSeq)

    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_029038.1 RefSeqGene

      Range
      5001..587070
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001037339.1 → NP_001032416.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4B isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant a. The resulting isoform (2, also referred to as PDE4B2 or PDE32) has a shorter and distinct N-terminus when compared to isoform 1.
      Source sequence(s)
      AW519027, BC046161, L20971, M97515
      Consensus CDS
      CCDS30743.1
      UniProtKB/Swiss-Prot
      Q07343
      UniProtKB/TrEMBL
      Q5TEK5
      Related
      ENSP00000360084, OTTHUMP00000010656, ENST00000371045, OTTHUMT00000025194
      Conserved Domains (2) summary
      cd00077
      Location:233 – 415
      Blast Score: 109
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      pfam00233
      Location:233 – 477
      Blast Score: 910
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    2. NM_001037340.1 → NP_001032417.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4B isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (c) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant a. The resulting isoform (3, also referred to as PDE4B3) has a shorter and distinct N-terminus when compared to isoform 1.
      Source sequence(s)
      AB209081, AW519027, BC036108, BC046161, BC101480
      Consensus CDS
      CCDS30742.1
      UniProtKB/Swiss-Prot
      Q07343
      UniProtKB/TrEMBL
      Q59GM8
      UniProtKB/TrEMBL
      Q5TEK4
      UniProtKB/TrEMBL
      Q5TEK6
      Related
      ENSP00000392947, OTTHUMP00000010654, ENST00000423207, OTTHUMT00000025190
      Conserved Domains (2) summary
      cd00077
      Location:390 – 572
      Blast Score: 118
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      pfam00233
      Location:390 – 634
      Blast Score: 934
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    3. NM_001037341.1 → NP_001032418.1  cAMP-specific 3',5'-cyclic phosphodiesterase 4B isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (d) has a 5' UTR that is further upstream than variant a. Both variants a and d encode the same isoform (1, also referred to as PDE4B1 or Tm72).
      Source sequence(s)
      AW519027, BC046161, BC071607, BC101480, DA103627
      Consensus CDS
      CCDS632.1
      UniProtKB/Swiss-Prot
      Q07343
      UniProtKB/TrEMBL
      Q5TEK6
      Related
      ENSP00000332116, OTTHUMP00000010652, ENST00000329654, OTTHUMT00000025188
      Conserved Domains (2) summary
      cd00077
      Location:405 – 587
      Blast Score: 119
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      pfam00233
      Location:405 – 649
      Blast Score: 937
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    4. NM_002600.3 → NP_002591.2  cAMP-specific 3',5'-cyclic phosphodiesterase 4B isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) encodes the longest isoform (1, also referred to as PDE4B1 or Tm72). Both variants a and d encode the same isoform.
      Source sequence(s)
      AA206316, AA453531, AW519027, BC046161, CN268011, DA126733, L20966
      Consensus CDS
      CCDS632.1
      UniProtKB/Swiss-Prot
      Q07343
      UniProtKB/TrEMBL
      Q5TEK6
      Related
      ENSP00000342637, OTTHUMP00000010653, ENST00000341517, OTTHUMT00000025189
      Conserved Domains (2) summary
      cd00077
      Location:405 – 587
      Blast Score: 119
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      pfam00233
      Location:405 – 649
      Blast Score: 937
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000001.10 Reference GRCh37.p5 Primary Assembly

      Range
      66258193..66840262
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000133.1 Alternate HuRef

      Range
      64366982..64949229
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL109926.9 CAI21748.1
      CAI21749.1
      CAI21750.1
      CAI21751.1
    genomic AL357273.18 CAH73002.1
      CAH73003.1
      CAH73004.1
    genomic AL357273.18 CAH73002.1
      CAH73003.1
      CAH73004.1
    genomic AL359701.27 CAI23099.1
      CAI23100.1
      CAI23101.1
    genomic AL513493.11 (99340..165779) None
    genomic AL590783.5 (2000..155357) None
    genomic AL591487.4 None
    genomic AL592285.7 CAH70626.1
      CAH70627.1
      CAH70628.1
    genomic CH471059.2 EAX06524.1
      EAX06525.1
    genomic GM837077.1 CAV28613.1
    mRNA AA206316.1 None
    mRNA AA453531.1 None
    mRNA AB209081.1 BAD92318.1
    mRNA AK000989.1 None
    mRNA AK127365.1 None
    mRNA AK289969.1 BAF82658.1
    mRNA AK290006.1 BAF82695.1
    mRNA AK290206.1 BAF82895.1
    mRNA AK294441.1 BAG57682.1
    mRNA AW519027.1 None
    mRNA BC036108.1 None
    mRNA BC046161.1 None
    mRNA BC071607.1 None
    mRNA BC101480.1 AAI01481.1
    mRNA BC105040.1 AAI05041.1
    mRNA CN268011.1 None
    mRNA CR749667.1 CAH18458.2
    mRNA DA103627.1 None
    mRNA DA126733.1 None
    mRNA EF595686.1 ABQ85407.1
    mRNA L12686.1 AAA35643.1
    mRNA L20966.1 AAA03589.1
    mRNA M97515.1 AAA36426.1
    mRNA U85048.1 AAB96381.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q07343.1 GenPept UniProtKB/Swiss-Prot:Q07343
    Q13945 GenPept UniProtKB/TrEMBL:Q13945
    Q59GM8 GenPept UniProtKB/TrEMBL:Q59GM8
    Q5TEK7 GenPept UniProtKB/TrEMBL:Q5TEK7
    Q68CX5 GenPept UniProtKB/TrEMBL:Q68CX5
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    Additional Links

    Gene LinkOut

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

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