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PDE8A phosphodiesterase 8A [ Homo sapiens (human) ]

Gene ID: 5151, updated on 7-Dec-2018

Summary

Official Symbol
PDE8Aprovided by HGNC
Official Full Name
phosphodiesterase 8Aprovided by HGNC
Primary source
HGNC:HGNC:8793
See related
Ensembl:ENSG00000073417 MIM:602972
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

Genomic context

See PDE8A in Genome Data Viewer
Location:
15q25.3
Exon count:
28
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 15 NC_000015.10 (84980513..85139145)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (85523744..85682376)

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 nucleolar protein interacting with the FHA domain of MKI67 pseudogene 8 Neighboring gene chondroitin sulfate proteoglycan 4 pseudogene 12

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

HIV-1 interactions

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 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...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ16150

Gene Ontology Provided by GOA

Function Evidence Code Pubs
3',5'-cyclic-AMP phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
3',5'-cyclic-AMP phosphodiesterase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
3',5'-cyclic-AMP phosphodiesterase activity TAS
Traceable Author Statement
more info
 
3',5'-cyclic-GMP phosphodiesterase activity IDA
Inferred from Direct Assay
more info
PubMed 
kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
cAMP catabolic process IEA
Inferred from Electronic Annotation
more info
 
cellular response to epidermal growth factor stimulus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to epidermal growth factor stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell death IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of hydrogen peroxide-induced cell death IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of ERK1 and ERK2 cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 

General protein information

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_016877797.1
XP_016877798.1
XP_016877799.1
XP_016877800.1
XP_024305714.1
XP_024305715.1

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_001243137.1NP_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
    Consensus CDS
    CCDS58397.1
    UniProtKB/Swiss-Prot
    O60658
    Related
    ENSP00000453808.1, ENST00000557957.5
    Conserved Domains (5) summary
    COG0745
    Location:1087
    OmpR; DNA-binding response regulator, OmpR family, contains REC and winged-helix (wHTH) domain [Signal transduction mechanisms, Transcription]
    cd00130
    Location:158252
    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:483735
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    pfam13426
    Location:154252
    PAS_9; PAS domain
    cl19078
    Location:1198
    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_002605.3NP_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
    O60658
    Related
    ENSP00000378056.1, ENST00000394553.5
    Conserved Domains (5) summary
    COG0745
    Location:82159
    OmpR; DNA-binding response regulator, OmpR family, contains REC and winged-helix (wHTH) domain [Signal transduction mechanisms, Transcription]
    cd00130
    Location:230324
    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:555807
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    pfam13426
    Location:226324
    PAS_9; PAS domain
    cl19078
    Location:83170
    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_173454.1NP_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:82159
    OmpR; DNA-binding response regulator, OmpR family, contains REC and winged-helix (wHTH) domain [Signal transduction mechanisms, Transcription]
    pfam00233
    Location:509761
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    cl19078
    Location:83170
    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: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p12 Primary Assembly

    Range
    84980513..85139145
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017022311.2XP_016877800.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X4

    UniProtKB/Swiss-Prot
    O60658
    UniProtKB/TrEMBL
    A0A024RC53
    Conserved Domains (3) summary
    cd00130
    Location:177
    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:308560
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    pfam13426
    Location:177
    PAS_9; PAS domain
  2. XM_017022308.2XP_016877797.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X1

  3. XM_017022310.2XP_016877799.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X3

  4. XM_017022309.1XP_016877798.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X2

    Conserved Domains (3) summary
    cd00130
    Location:40134
    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:365617
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
    pfam13426
    Location:36134
    PAS_9; PAS domain
  5. XM_024449946.1XP_024305714.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X6

    Conserved Domains (1) summary
    pfam00233
    Location:175426
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  6. XM_011521668.2XP_011519970.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X5

    Conserved Domains (1) summary
    pfam00233
    Location:297549
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase
  7. XM_024449947.1XP_024305715.1  high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A isoform X6

    Conserved Domains (1) summary
    pfam00233
    Location:175426
    PDEase_I; 3'5'-cyclic nucleotide phosphodiesterase

RNA

  1. XR_001751313.2 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.
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