Human Gene PDE8A (uc010bnc.3) Description and Page Index
  Description: Homo sapiens phosphodiesterase 8A (PDE8A), transcript variant 1, mRNA.
RefSeq Summary (NM_002605): 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].
Transcript (Including UTRs)
   Position: hg19 chr15:85,525,205-85,682,376 Size: 157,172 Total Exon Count: 23 Strand: +
Coding Region
   Position: hg19 chr15:85,634,302-85,681,134 Size: 46,833 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr15:85,525,205-85,682,376)mRNA (may differ from genome)Protein (582 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: PDE8A_HUMAN
DESCRIPTION: RecName: Full=High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A; EC=3.1.4.17;
FUNCTION: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development.
CATALYTIC ACTIVITY: Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate.
COFACTOR: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
ENZYME REGULATION: Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and zaprinast as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP.
PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
TISSUE SPECIFICITY: Expressed in most tissues except thymus and peripheral blood leukocytes. Highest levels in testis, ovary, small intestine and colon.
DOMAIN: Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.
SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.
SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain.
SIMILARITY: Contains 1 PAS (PER-ARNT-SIM) domain.
SEQUENCE CAUTION: Sequence=AAL18612.1; Type=Erroneous translation; Note=Wrong choice of CDS; Sequence=AAL18613.1; Type=Erroneous translation; Note=Wrong choice of CDS; Sequence=AAL18614.1; Type=Erroneous translation; Note=Wrong choice of CDS; Sequence=BAG54458.1; Type=Miscellaneous discrepancy; Note=Intron retention; Sequence=EAX01967.1; Type=Erroneous gene model prediction;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PDE8A
CDC HuGE Published Literature: PDE8A
Positive Disease Associations: Glucose , Myocardial Infarction
Related Studies:
  1. Glucose
    , , . [PubMed 0]
  2. Myocardial Infarction
    , , . [PubMed 0]
  3. Myocardial Infarction
    , , . [PubMed 0]
           more ... click here to view the complete list

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.90 RPKM in Colon - Transverse
Total median expression: 554.87 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -444.801128-0.394 Picture PostScript Text
3' UTR -300.031242-0.242 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003607 - HD/PDEase_dom
IPR000014 - PAS
IPR013767 - PAS_fold
IPR023088 - PDEase
IPR002073 - PDEase_catalytic_dom
IPR023174 - PDEase_CS
IPR001789 - Sig_transdc_resp-reg_receiver

Pfam Domains:
PF00233 - 3'5'-cyclic nucleotide phosphodiesterase
PF13426 - PAS domain

SCOP Domains:
109604 - HD-domain/PDEase-like
55785 - PYP-like sensor domain (PAS domain)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1LHQ
- Model

1LXX
- Model

3ECM
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3ECN - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O60658
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
GO:0008081 phosphoric diester hydrolase activity
GO:0016787 hydrolase activity
GO:0019900 kinase binding
GO:0046872 metal ion binding

Biological Process:
GO:0001934 positive regulation of protein phosphorylation
GO:0006198 cAMP catabolic process
GO:0006355 regulation of transcription, DNA-templated
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0009187 cyclic nucleotide metabolic process
GO:0060548 negative regulation of cell death
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071364 cellular response to epidermal growth factor stimulus
GO:1903206 negative regulation of hydrogen peroxide-induced cell death

Cellular Component:
GO:0005829 cytosol
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  LF207743 - JP 2014500723-A/15246: Polycomb-Associated Non-Coding RNAs.
BC060762 - Homo sapiens phosphodiesterase 8A, mRNA (cDNA clone MGC:71504 IMAGE:30344110), complete cds.
AK074280 - Homo sapiens cDNA FLJ23700 fis, clone HEP10682, highly similar to Homo sapiens cAMP-specific cyclic nucleotide phosphodiesterase PDE8A1 mRNA.
AF388183 - Homo sapiens cAMP phosphodiesterase PDE8A1 mRNA, complete cds, alternatively spliced.
AF388184 - Homo sapiens cAMP phosphodiesterase PDE8A2 mRNA, complete cds, alternatively spliced.
AF388185 - Homo sapiens cAMP phosphodiesterase PDE8A3 mRNA, complete cds, alternatively spliced.
AF388186 - Homo sapiens cAMP phosphodiesterase PDE8A4 mRNA, complete cds, alternatively spliced.
AF388187 - Homo sapiens cAMP phosphodiesterase PDE8A5 mRNA, complete cds, alternatively spliced.
AF332653 - Homo sapiens cAMP-specific cyclic nucleotide phosphodiesterase PDE8A1 mRNA, complete cds.
BC036190 - Homo sapiens cDNA clone IMAGE:5272367, containing frame-shift errors.
BC075822 - Homo sapiens phosphodiesterase 8A, mRNA (cDNA clone MGC:88492 IMAGE:6296489), complete cds.
MA443320 - JP 2018138019-A/15246: Polycomb-Associated Non-Coding RNAs.
LF212122 - JP 2014500723-A/19625: Polycomb-Associated Non-Coding RNAs.
MA447699 - JP 2018138019-A/19625: Polycomb-Associated Non-Coding RNAs.
AK127232 - Homo sapiens cDNA FLJ45299 fis, clone BRHIP3003644, highly similar to High-affinity cAMP-specific andIBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC 3.1.4.17).
AF056490 - Homo sapiens cAMP-specific phosphodiesterase 8A (PDE8A) mRNA, partial cds.
LF368573 - JP 2014500723-A/176076: Polycomb-Associated Non-Coding RNAs.
LF368574 - JP 2014500723-A/176077: Polycomb-Associated Non-Coding RNAs.
BC048317 - Homo sapiens phosphodiesterase 8A, mRNA (cDNA clone IMAGE:4515899), partial cds.
AK122689 - Homo sapiens cDNA FLJ16150 fis, clone BRAMY2044838, highly similar to High-affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (EC 3.1.4.17).
BC013825 - Homo sapiens phosphodiesterase 8A, mRNA (cDNA clone IMAGE:3866625).
BC037260 - Homo sapiens phosphodiesterase 8A, mRNA (cDNA clone IMAGE:3866602).
AL109778 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1130787.
AL109687 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 289972.
BC017164 - Homo sapiens phosphodiesterase 8A, mRNA (cDNA clone IMAGE:3921020), partial cds.
AL109789 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 40237.
JD314994 - Sequence 296018 from Patent EP1572962.
JD146151 - Sequence 127175 from Patent EP1572962.
MA604150 - JP 2018138019-A/176076: Polycomb-Associated Non-Coding RNAs.
MA604151 - JP 2018138019-A/176077: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00230 - Purine metabolism

Reactome (by CSHL, EBI, and GO)

Protein O60658 (Reactome details) participates in the following event(s):

R-HSA-418553 cAMP degradation by Phosphodiesterases
R-HSA-418555 G alpha (s) signalling events
R-HSA-388396 GPCR downstream signalling
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: AF388187, B3KXE6, NM_002605, NP_002596, O60658, PDE8A_HUMAN, Q6P9H3, Q969I1, Q96PC9, Q96PD0, Q96PD1, Q96T71, Q9UMB7, Q9UMC3
UCSC ID: uc010bnc.3
RefSeq Accession: NM_002605
Protein: O60658 (aka PDE8A_HUMAN or CN8A_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AF388187.1
exon count: 23CDS single in 3' UTR: no RNA size: 2999
ORF size: 1749CDS single in intron: no Alignment % ID: 99.87
txCdsPredict score: 2708.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.