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    PDE8A phosphodiesterase 8A [ Homo sapiens (human) ]

    Gene ID: 5151, updated on 16-Apr-2024

    Summary

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    Official Symbol
    PDE8Aprovided by HGNC
    Official Full Name
    phosphodiesterase 8Aprovided by HGNC
    Primary source
    HGNC:HGNC:8793
    See related
    Ensembl:ENSG00000073417 MIM:602972; AllianceGenome:HGNC:8793
    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
    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]
    Expression
    Ubiquitous expression in colon (RPKM 9.5), kidney (RPKM 8.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    15q25.3
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (84980467..85139142)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (82732711..82891368)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (85523698..85682373)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene solute carrier family 28 member 1 Neighboring gene RNA, U6 small nuclear 796, pseudogene Neighboring gene high mobility group box 1 pseudogene 43 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_41947 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:85522585-85523086 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:85523087-85523586 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6775 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:85524736-85525268 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9996 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9997 Neighboring gene Sharpr-MPRA regulatory region 10787 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6777 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9998 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9999 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10000 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10001 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_41972 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_42025 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:85668261-85668811 Neighboring gene uncharacterized LOC124903545 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_42032 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:85708039-85708575 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6778 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:85741901-85742401 Neighboring gene NIFK pseudogene 8 Neighboring gene chondroitin sulfate proteoglycan 4 pseudogene 12

    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. Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications. Salvetat N, et al. Transl Psychiatry, 2021 Apr 30. PMID 33931591, Free PMC Article
    2. Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents. Chimienti F, et al. Transl Psychiatry, 2019 Feb 15. PMID 30770787, Free PMC Article
    3. Phosphodiesterase 8a supports HIV-1 replication in macrophages at the level of reverse transcription. Booiman T, et al. PLoS One, 2014. PMID 25295610, Free PMC Article
    4. Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling. Krishnamurthy S, et al. Biophys J, 2014 Sep 16. PMID 25229150, Free PMC Article
    5. Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation. Brown KM, et al. FEBS Lett, 2012 Jun 4. PMID 22673573

    See all (44) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 14-3-3 interaction with phosphodiesterase 8A sustains PKA signaling and downregulates the MAPK pathway.
      Title: 14-3-3 interaction with phosphodiesterase 8A sustains PKA signaling and downregulates the MAPK pathway.
    2. cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor.
      Title: cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor.
    3. Phosphodiesterase 8A Regulates CFTR Activity in Airway Epithelial Cells.
      Title: Phosphodiesterase 8A Regulates CFTR Activity in Airway Epithelial Cells.
    4. Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications.
      Title: Phosphodiesterase 8A to discriminate in blood samples depressed patients and suicide attempters from healthy controls based on A-to-I RNA editing modifications.
    5. Editing of PDE8A mRNA displayed clear regional difference when comparing dorsolateral prefrontal cortex (BA9) and anterior cingulate cortex (BA24). There were significant intra-regional differences between non-psychiatric control individuals and depressed suicide decedents.
      Title: Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents.
    6. PDE8 is expressed in lipid rafts of human airway smooth muscle cells(HASM), where it specifically regulates beta2-adrenergic receptor/ AC6 signaling to modulate HASM responsiveness and airway remodeling in asthma.
      Title: PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by β(2)-Adrenergic Receptors and Adenylyl Cyclase 6.
    7. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq
      Title: Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape.
    8. PDE8A supports HIV-1 replication in macrophages
      Title: Phosphodiesterase 8a supports HIV-1 replication in macrophages at the level of reverse transcription.
    9. a novel and critical role for phosphodiesterases in moderating local concentrations of cAMP in microdomains and signal resetting
      Title: Active site coupling in PDE:PKA complexes promotes resetting of mammalian cAMP signaling.
    10. PDE8A can bind tightly to Raf-1, regulate Raf-1 phosphorylation on S259, and, in so doing, regulate the cross-talk node whereby cAMP exerts an inhibitory effect on Raf-1 signaling, retarding subsequent ERK phosphorylation and activation.
      Title: Phosphodiesterase-8A binds to and regulates Raf-1 kinase.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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

    EBI GWAS Catalog

    Description
    Genetic variants associated with disordered eating.
    EBI GWAS Catalog
    New loci associated with central cornea thickness include COL5A1, AKAP13 and AVGR8.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 replication is enhanced by PDE8A PubMed
    shRNA knockdown of PDE8A decreases HIV-1 replication in primary monocytes; HIV-1 replication is enhanced by PDE8A PubMed
    Knockdown of phosphodiesterase 8A (PDE8A) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    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 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

    Clone Names

    • FLJ16150

    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 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables 3',5'-cyclic-GMP phosphodiesterase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3',5'-cyclic-GMP phosphodiesterase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein kinase activator activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    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 epidermal growth factor stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to epidermal growth factor stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of ERK1 and ERK2 cascade IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of DNA-templated transcription IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in perinuclear region of cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A
    Names
    cAMP-specific cyclic nucleotide phosphodiesterase 8A
    NP_001230066.1
    NP_002596.1
    NP_775656.1
    XP_011519970.1
    XP_016877799.1
    XP_047288612.1
    XP_047288613.1
    XP_047288614.1
    XP_047288615.1
    XP_047288616.1
    XP_047288617.1
    XP_054234150.1
    XP_054234151.1
    XP_054234152.1
    XP_054234153.1
    XP_054234154.1
    XP_054234155.1
    XP_054234156.1
    XP_054234157.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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
      6344..163630
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243137.2 → 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)
      AC087468, AF388183, AK074280, BC060762
      Consensus CDS
      CCDS58397.1
      UniProtKB/Swiss-Prot
      O60658
      Related
      ENSP00000453808.1, ENST00000557957.5
      Conserved Domains (5) summary
      COG0745
      Location:10 → 87
      OmpR; DNA-binding response regulator, OmpR family, contains REC and winged-helix (wHTH) domain [Signal transduction mechanisms, Transcription]
      cd00130
      Location:158 → 252
      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 → 735
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam13426
      Location:154 → 252
      PAS_9; PAS domain
      cl19078
      Location:11 → 98
      REC; Signal receiver domain; originally thought to be unique to bacteria (CheY, OmpR, NtrC, and PhoB), now recently identified in eukaroytes ETR1 Arabidopsis thaliana; this domain receives the signal from the sensor partner in a two-component systems; ...

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

      See identical proteins and their annotated locations for NP_002596.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longest isoform (1).
      Source sequence(s)
      AC087468, AF388183, BC060762
      Consensus CDS
      CCDS10336.1
      UniProtKB/Swiss-Prot
      B3KXE6, H0YMZ7, O60658, Q6P9H3, Q969I1, Q96PC9, Q96PD0, Q96PD1, Q96T71, Q9UMB7, Q9UMC3
      Related
      ENSP00000378056.1, ENST00000394553.6
      Conserved Domains (5) summary
      COG0745
      Location:82 → 159
      OmpR; DNA-binding response regulator, OmpR family, contains REC and winged-helix (wHTH) domain [Signal transduction mechanisms, Transcription]
      cd00130
      Location:230 → 324
      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 → 807
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      pfam13426
      Location:226 → 324
      PAS_9; PAS domain
      cl19078
      Location:83 → 170
      REC; Signal receiver domain; originally thought to be unique to bacteria (CheY, OmpR, NtrC, and PhoB), now recently identified in eukaroytes ETR1 Arabidopsis thaliana; this domain receives the signal from the sensor partner in a two-component systems; ...

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

      See identical proteins and their annotated locations for NP_775656.1

      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
      ENSP00000340679.5, ENST00000339708.9
      Conserved Domains (3) summary
      COG0745
      Location:82 → 159
      OmpR; DNA-binding response regulator, OmpR family, contains REC and winged-helix (wHTH) domain [Signal transduction mechanisms, Transcription]
      pfam00233
      Location:509 → 761
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
      cl19078
      Location:83 → 170
      REC; Signal receiver domain; originally thought to be unique to bacteria (CheY, OmpR, NtrC, and PhoB), now recently identified in eukaroytes ETR1 Arabidopsis thaliana; this domain receives the signal from the sensor partner in a two-component systems; ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      84980467..85139142
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432657.1 → XP_047288613.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X2

    2. XM_017022310.3 → XP_016877799.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X4

    3. XM_047432661.1 → XP_047288617.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X8

    4. XM_047432656.1 → XP_047288612.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1

    5. XM_047432658.1 → XP_047288614.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X3

    6. XM_047432660.1 → XP_047288616.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X7

    7. XM_047432659.1 → XP_047288615.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X5

    8. XM_011521668.3 → XP_011519970.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X6

      Conserved Domains (1) summary
      pfam00233
      Location:297 → 549
      PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

    RNA

    1. XR_007064457.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      82732711..82891368
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054378176.1 → XP_054234151.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X2

    2. XM_054378178.1 → XP_054234153.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X4

    3. XM_054378182.1 → XP_054234157.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X8

    4. XM_054378175.1 → XP_054234150.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1

    5. XM_054378177.1 → XP_054234152.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X3

    6. XM_054378181.1 → XP_054234156.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X7

    7. XM_054378179.1 → XP_054234154.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X5

    8. XM_054378180.1 → XP_054234155.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X6

    RNA

    1. XR_008488965.1 RNA Sequence

    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.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O60658.2 GenPept UniProtKB/Swiss-Prot:O60658

    Gene LinkOut

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

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