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    PDE8A phosphodiesterase 8A [ Homo sapiens ]

    Gene ID: 5151, updated on 19-May-2012
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    Summary

    Official Symbol
    PDE8Aprovided by HGNC
    Official Full Name
    phosphodiesterase 8Aprovided by HGNC
    Primary source
    HGNC:8793
    See related
    Ensembl:ENSG00000073417; HPRD:09114; MIM:602972; Vega:OTTHUMG00000148670
    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
    HsT19550; FLJ16150
    Summary
    The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE8 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 found for this gene.[provided by RefSeq, Jul 2011]
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    Genomic context

    Location :
    15q25.3
    Sequence :
    Chromosome: 15; NC_000015.9 (85525205..85682373)
    See PDE8A in Epigenomics, MapViewer

    Chromosome 15 - NC_000015.9Genomic Context describing neighboring genes Neighboring gene alpha-kinase 3 Neighboring gene solute carrier family 28 (sodium-coupled nucleoside transporter), member 1 Neighboring gene high mobility group box 1 pseudogene 43 Neighboring gene MKI67 (FHA domain) interacting nucleolar phosphoprotein pseudogene Neighboring gene chondroitin sulfate proteoglycan 4 pseudogene

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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. Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages. Bol SM, et al. Virology, 2011 Nov 10. PMID 21920574.
    2. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    3. New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8. Vitart V, et al. Hum Mol Genet, 2010 Nov 1. PMID 20719862.
    4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. Bailey SD, et al. Diabetes Care, 2010 Oct. PMID 20628086.
    5. Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. Talmud PJ, et al. Am J Hum Genet, 2009 Nov. PMID 19913121.

    See all (18) 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. Polymorphism in PDE8A affects HIV-1 replication in primary macrophages.
      Title: Polymorphism in HIV-1 dependency factor PDE8A affects mRNA level and HIV-1 replication in primary macrophages.
    2. 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.
    3. The findings exclude a significant role for PDE8A as a PCOS candidate gene, and as a Las major determinant of androgen levels in women.
      Title: PDE8A genetic variation, polycystic ovary syndrome and androgen levels in women.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
    5. kinetic properties of the highly active PDE8A1 catalytic domain prepared from refolding and its crystal structures in the unliganded and 3-isobutyl-1-methylxanthine (IBMX) bound forms at 1.9 and 2.1 A resolutions
      Title: Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity.
    6. Comparison of enzymatic characterization and gene organization of PDE8B and PDE8A.
      Title: Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in humans.
    7. in vitro and in vivo experiments demonstrated that the association with IkappaB greatly enhanced the enzyme activity of PDE8A1
      Title: Per-Arnt-Sim domain-dependent association of cAMP-phosphodiesterase 8A1 with IkappaB proteins.
    Submit: New GeneRIF Correction
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8.

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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

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    BioGRID:111177 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • 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 ...
    • 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
    		  
    3',5'-cyclic-nucleotide phosphodiesterase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    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
    		  
    two-component response regulator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    cyclic nucleotide metabolic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    regulation of transcription, DNA-dependent IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cellular_component ND
    No biological Data available
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
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    General protein information

    Preferred Names
    high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
    Names
    high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
    cAMP-specific cyclic nucleotide phosphodiesterase 8A
    NP_002596.1
    NP_775656.1
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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_029630.1 RefSeqGene

      Range
      5001..163633
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243137.1 → NP_001230066.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an in-frame downstream AUG, and an isoform (3) with a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AF388183, AI767983, AK074280, BC060762
      UniProtKB/TrEMBL
      H0YMZ7
      UniProtKB/Swiss-Prot
      O60658
      Conserved Domains (5) summary
      cd00077
      Location:483 – 677
      Blast Score: 107
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      cd00130
      Location:154 – 252
      Blast Score: 117
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00233
      Location:483 – 737
      Blast Score: 539
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam00072
      Location:10 – 126
      Blast Score: 127
      Response_reg; Response regulator receiver domain
      pfam13426
      Location:158 – 252
      Blast Score: 148
      PAS_9; PAS domain

    2. NM_002605.2 → NP_002596.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longest isoform (1).
      Source sequence(s)
      AF388183, BC060762
      Consensus CDS
      CCDS10336.1
      UniProtKB/Swiss-Prot
      O60658
      Related
      ENSP00000378056, ENST00000394553
      Conserved Domains (5) summary
      cd00077
      Location:555 – 749
      Blast Score: 108
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      cd00130
      Location:226 – 324
      Blast Score: 118
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam00233
      Location:555 – 809
      Blast Score: 543
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam00072
      Location:82 – 198
      Blast Score: 127
      Response_reg; Response regulator receiver domain
      pfam13426
      Location:230 – 324
      Blast Score: 149
      PAS_9; PAS domain

    3. NM_173454.1 → NP_775656.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1. This results in a shorter isoform (2) missing an internal protein segment compared to isoform 1.
      Source sequence(s)
      AF388184, BC060762
      Consensus CDS
      CCDS10337.1
      UniProtKB/Swiss-Prot
      O60658
      Related
      ENSP00000340679, OTTHUMP00000192899, ENST00000339708, OTTHUMT00000309019
      Conserved Domains (3) summary
      cd00077
      Location:509 – 703
      Blast Score: 108
      HDc; Metal dependent phosphohydrolases with conserved 'HD' motif
      pfam00233
      Location:509 – 763
      Blast Score: 541
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam00072
      Location:82 – 198
      Blast Score: 127
      Response_reg; Response regulator receiver domain

    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_000015.9 Reference GRCh37.p5 Primary Assembly

      Range
      85525205..85682373
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000147.1 Alternate HuRef

      Range
      61611075..61768258
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_173455.1: Suppressed sequence

      Description
      NM_173455.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    2. NM_173456.1: Suppressed sequence

      Description
      NM_173456.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    3. NM_173457.1: Suppressed sequence

      Description
      NM_173457.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC027078.6 (43036..131739) None
    genomic AC087468.11 None
    genomic AF388188.1 None
    genomic CH471101.1 EAX01965.1
      EAX01966.1
      EAX01967.1
      EAX01968.1
      EAX01969.1
      EAX01970.1
    mRNA AF056490.1 AAC39763.1
    mRNA AF332653.1 AAK57641.1
    mRNA AF388183.1 AAL18610.1
    mRNA AF388184.1 AAL18611.1
    mRNA AF388185.1 AAL18612.1
    mRNA AF388186.1 AAL18613.1
    mRNA AF388187.1 AAL18614.1
    mRNA AI767983.1 None
    mRNA AK074280.1 None
    mRNA AK122689.1 BAG53669.1
    mRNA AK127232.1 BAG54458.1
    mRNA AL109687.1 CAB52020.1
    mRNA AL109778.1 CAB52432.1
    mRNA AL109789.1 CAB52453.1
    mRNA BC013825.1 None
    mRNA BC017164.2 None
    mRNA BC036190.1 None
    mRNA BC037260.1 None
    mRNA BC048317.1 AAH48317.1
    mRNA BC060762.1 AAH60762.1
    mRNA BC075822.1 AAH75822.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60658.2 GenPept UniProtKB/Swiss-Prot:O60658
    Q86XV4 GenPept UniProtKB/TrEMBL:Q86XV4
    Q9UMB5 GenPept UniProtKB/TrEMBL:Q9UMB5
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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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