Information on EC 3.1.4.53 - 3',5'-cyclic-AMP phosphodiesterase and Organism(s) Rattus norvegicus and UniProt Accession P14270

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Rattus norvegicus
UNIPROT: P14270
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria


The taxonomic range for the selected organisms is: Rattus norvegicus

EC NUMBER
COMMENTARY hide
3.1.4.53
-
RECOMMENDED NAME
GeneOntology No.
3',5'-cyclic-AMP phosphodiesterase
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Purine metabolism
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-
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-AMP 5'-nucleotidohydrolase
Requires Mg2+ or Mn2+ for activity [2]. This enzyme is specific for 3',5'-cAMP and does not hydrolyse other nucleoside 3',5'-cyclic phosphates such as cGMP (cf. EC 3.1.4.17, 3,5-cyclic-nucleotide phosphodiesterase and EC 3.1.4.35, 3,5-cyclic-GMP phosphodiesterase). It is involved in modulation of the levels of cAMP, which is a mediator in the processes of cell transformation and proliferation [3].
CAS REGISTRY NUMBER
COMMENTARY hide
9036-21-9
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Sprague-Dawley, male
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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effects of acute hypoxia on cAMP accumulation induced by PDE inhibitors in oxygen-specific chemosensors, the carotid bodies and in non-chemosensitive CB-related structures: carotid arteries and superior cervical ganglia, overview. Acute hypoxia enhances the effects of IBMX and PDE4 inhibitors on cAMP accumulation in carotid arteries and bodies, while in superior cervical ganglia In SCG, acute hypoxia reduces cAMP accumulation induced by all the four PDE inhibitors
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
P14646
PDE4B4 isoform may have a distinct functional role in regulating cAMP levels in specific cell types
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
the enzyme is able to use Mg2+, Co2+, and Mn2+, but not Zn2+
Mg2+
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the enzyme is able to use Mg2+, Co2+, and Mn2+, but not Zn2+
Mn2+
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0.015 mM, 20fold increase in activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-isobutyl-1-methylxanthine
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-
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
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Ro-20-1724
4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone
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competitive
8-(4-chlorophenyl)thioguanosine 3',5'-cyclic monophosphate
-
-
8-bromoguanosine 3',5'-cyclic monophosphate
-
-
CI-1044
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i.e. (R)-N-[9-amino-3,4,6,7-tetrahydro-4-oxo-1-phenylpyrrolo[3,2,1-j,k][1,4] benzodiazepin-3-yl]-3-pyridinecarboxamide, selective inhibitor of PDE4, administration of 160 mg/kg of CI-1044 causes perivascular and interstitial inflammation, with infiltrates of admixed neutrophils and macrophages but without evidence of vascular necrosis, PDE4 inhibitor CI-1044 induces changes of vascular tone that could lead to histological alterations in the mesenteric area
DC-TA 46
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the inhibitor affects memory retention in a visible/hidden-platform water maze task. This memory impairment can be correlated to the decrease of cAMP nucleotide, due to the induction of a PDE4D cAMP-specific PDE isoform
dexamethasone
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dexmethasone at 0.1 mg/kg inhibits the activity of PDE4
erythro-9-(2-hydroxy-3-nonyl)adenine
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a PDE2 selective inhibitor
isobutylmethylxanthine
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a non-specific PDE inhibitor
L-826,141
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PDE4-selective inhibitor
methylisobutylxanthine
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roflumilast
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PDE4-selective inhibitor
rolipram
theophylline
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non-selective inhibitor of phosphodiesterases
vardenafil
-
PDE5 inhibitor
XAP2
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noncompetitive inhibition, aryl-hydrocarbon receptor-interacting protein XAP2 inhibits PDE4A5 activity by XAP2 does not require any intermediate proteins. XAP2 inhibits PDE4A5 and not other PDE4 isoforms
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Zl-n-91
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selective PDE4 inhibitor, Zl-n-91 at 0.03, 0.3 or 3 mg/kg dose dependently inhibits PDE4 activity
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
extract of Ginkgo biloba
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some beneficial effects of extract of Ginkgo biloba might be due to its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE
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follicle-stimulating hormone
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stimulation
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haloperidol
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chronic treatment with 20 mg/kg clozapine increases PDE4B2 and PDE4B4 expression by 102 and 71%, respectively
additional information
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PDE4B1, PDE4B2, PDE4B3, and PDE4B4 are not changed by chronic haloperidol treatment
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0054
adenosine 3',5'-cyclic phosphate
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0018
4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone
-
-
0.074
rolipram
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-
0.000099
XAP2
-
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0005
CI-1044
Rattus norvegicus;
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pH and temperature not specified in the publication
0.0000004 - 0.0000013
L-826,141
0.04
methylisobutylxanthine
Rattus norvegicus;
-
-
0.002
Ro20-1724
Rattus norvegicus;
-
-
0.0000001 - 0.0000006
roflumilast
0.000083 - 0.001
rolipram
0.000117
SB 207499
Rattus norvegicus;
P14270, P14646
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0.000109
SCH 351591
Rattus norvegicus;
P14270, P14646
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.7
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isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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age-related increases in isoforms PDE8A3, PDE8A4/5 protein expression are confirmed in hippocampus of old versus young rodents. Relative to young rats, the hippocampi of old rats demonstrate strikingly decreased phosphorylation of GluR1, CaMKIIalpha, and CaMKIIbeta, decreased expression of the transmembrane AMPA regulatory proteins gamma2 (a.k.a. stargazin) and gamma8, and increased trimethylation of H3K27. Expression of isoforms of PDE8A4/5, PDE8A3 correlate with these functional endpoints in young but not old rats
Manually annotated by BRENDA team
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the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive rats, and Dahl salt-resistant rats, phosphodiesterase 4B expression is detected in the renal vasculature, proximal tubules, and distal tubules
Manually annotated by BRENDA team
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immature cell. Almost all PDE4D variants are expressed throughout the early postpartum period with a specific increase in PDE4 activity in both soluble and particulate fraction of 20 day old Sertoli cells; isolated from 10-, 20-, and 30-days-old rats. Specific increase in PDE4 activity in both the soluble and particulate subcellular fractions of 20-days-old Sertoli cells. Almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH. The subcellular distribution and expression of PDE4D proteins are unaffected by the developmental status of the Sertoli cells. Only the expression of short PDE4D1 appears to be upregulated by FSH and only in 20-days-old Sertoli cells, which suggests phenotype-dependent differential regulation of Pde4d1 mRNA translation
Manually annotated by BRENDA team
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PDE4 is present in young and adult gland. During development PDE4 is the major PDE
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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PDE4A splice variant RD1 contains a membrane-association signal which allows the targeted expression of RD1 within the Golgi complex of human follicular thyroid carcinoma cell lines FTC133 and FTC236
Manually annotated by BRENDA team
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short variant PDE4D1 is mainly particulate
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Manually annotated by BRENDA team
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long variants of PDE4D are mainly soluble
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Manually annotated by BRENDA team
additional information
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the soluble PDE4 activities are mainly related to the long PDE4D isoforms and short PDE4D1 is predominantly particulate
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
58000
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PDE4B4 recombinant protein, SDS-PAGE
62000
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unphosphorylated PDE4B4
66000
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phosphorylated PDE4B4
69000
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PDE4B2 recombinant protein, SDS-PAGE
87000
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PDE4B1 or PDE4B3 recombinant protein, SDS-PAGE, the 87000 Da band is termed PDE4B1/B3 due to difficulty of resolving it into separate bands using SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GST-rPDE4D1 fusion protein
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cells of two human follicular thyroid carcinoma cell lines (FTC133, FTC236) are stably transfected with a cDNA encoding the PDE4A cAMP-specific phosphodiesterase (PDE) splice variant RD1 (RNPDE4A1A) so as to generate the cloned cell lines, FTC133A and FTC236A
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expressed in COS-1 cells
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expressed in HEK-293 cells
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expressed in Rattus norvegicus INS-1 832/13 cell line
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expression in COS1 cells
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expression in COS7 cells
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expression of PDE4B4 cDNA in COS7 cells. Treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which is associated with the phosphorylation of PDE4B4 on Ser56 within UCR1
full coding sequence of the phosphodiesterase PDE4D1 is inserted in the bacterial expression vector pGEX-KG. N- and C-terminal truncations are also placed in the same vector, allowing the expression and purification of glutathione S-transferase (GST)-PDE fusion proteins using glutathione-Sepharose
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
forskolin treatment alone is unable to stimulate mAKAP-bound PDE4D3 activity significantly in HEK-293 cells, whereas forskolin (0.05 mM) and okadaic acid (0.3 mM) treatment together synergistically increase PDE4D3 activity
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isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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PDE5 inhibition improved short-term object recognition performance after an acute tryptophan depletion induced deficit
molecular biology
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convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE4; convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE7; convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE8