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Information on EC 3.1.4.35 - 3',5'-cyclic-GMP phosphodiesterase and Organism(s) Mus musculus and UniProt Accession O70628
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3.1.4.35 3',5'-cyclic-GMP phosphodiesteraseSpecify your search results
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
phosphodiesterase type 5, phosphodiesterase-5, pde-5, phosphodiesterase 5, cgmp phosphodiesterase, pde5a, cyclic gmp phosphodiesterase, phosphodiesterase type-5, pde6b, cgmp-phosphodiesterase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3',5'-cyclic GMP phosphodiesterase
-
-
-
-
cGMP phosphodiesterase
cGMP-PDE
cyclic 3',5'-GMP phosphodiesterase
-
-
-
-
cyclic GMP phosphodiesterase
-
-
-
-
cyclic guanosine 3',5'-monophosphate phosphodiesterase
-
-
-
-
cyclic guanosine 3',5'-phosphate phosphodiesterase
-
-
-
-
guanosine cyclic 3',5'-phosphate phosphodiesterase
-
-
-
-
PDE5
PDEgamma
-
the inhibitory subunit of the retinal cGMP phosphodiesterase 6 is a critical regulator of phototransduction
phosphodiesterase cGMP
-
-
-
-
phosphodiesterase, guanosine cyclic 3',5'-phosphate
-
-
-
-
cGMP phosphodiesterase
-
-
-
-
cGMP-PDE
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-GMP 5'-nucleotidohydrolase
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CAS REGISTRY NUMBER
COMMENTARY
9068-52-4
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
PDE5A has a higher selectivity for cGMP due to much lower cAMP binding affinity
-
-
?
additional information
?
-
-
PDE5 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
?
additional information
?
-
-
interaction between the PDE6 gamma subunit with tubulin alpha and beta, specificity and mechanism, detailed overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
-
-
?
additional information
?
-
-
PDE5 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
?
additional information
?
-
-
interaction between the PDE6 gamma subunit with tubulin alpha and beta, specificity and mechanism, detailed overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
i.e. BAY 73-6691, IC50: 100 nM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
alpha-subunit of transducin
-
in presence of transducin alpha-subunit-GTP, the inhibitory gamma subunit of PDE6 remains attached to the rest of the PDE6 molecule, but after conversion to transducin alpha-subunit-GDP, the PDE6 gamma subunit may dissociate from PDE6 and exchange with a cytoplasmic pool
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light
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light stimulates PDE6 activation, rapid reduction in cGMP, closure of Na+/Ca2+ channels and reduced Ca2+ influx
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0012
5-(2-propoxyphenyl)-2,3-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
Mus musculus
i.e. BAY 73-6691, IC50: 100 nM
0.00267
carboxyamidotriazole
Mus musculus
-
enzyme from peritoneal macrophage, at pH 8.0 and 30°C
0.00898
carboxyamidotriazole
Mus musculus
-
enzyme from Lewis lung carcinoma cells, at pH 8.0 and 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in the vasculature, PDE5 is the predominant PDE isoform involved in degrading cGMP
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PDE5 is induced in neuroblastoma-glioma NG108-15 cells after dibutyryl treatment
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PDE5 is present in cumulus cells of big, antral follicles
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isoform PDE5A shows 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 isoform PDE9A does not change with age. Age-related increases in PDE11A4, and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents, as are age-related increases in PDE8A3 protein expression in the striatum
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
during rod phototransduction, cGMP and Ca2+ are regulated by PDE6, guanylate cyclase, and cGMP-gated Na+/Ca2+ channels. The level of cGMP is controlled by opposing activities of PDE6 and guanylate cyclase and, at sufficiently high levels, Na+/Ca2+ channels open to allow increased Ca2+ influx into the rod outer segment
physiological function
-
PDE6 consistis of catalytic alpha and beta subunits and two inhibitory gamma subunits, molecular mechanism of PDE6gamma regulation of the catalytic subunits, overview. Ile86 and Ile87 residues are necessary for normal inhibition of PDE6 catalytic activity in vivo, and increased basal activity of PDE can be partially compensated by GCAP-dependent regulation of guanylyl cyclase
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDE9A_MOUSE
534
0
61636
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
182000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
additional information
-
binding sites of catalytic subunits alpha and beta of PDE6 are accessible to excess inhibitory subunit gamma in the light, once endogenous gamma subunit has been displaced from its binding site by transducin alpha-subunit-GTP
tetramer
-
alphabeta(gamma)2,PDE6 consistis of catalytic alpha and beta subunits and two inhibitory gamma subunits
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D196A
the mutation disrupts cGMP binding and increases cAMP affinity in constructs containing only GAF (mammalian cGMP-dependent PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA), causing an altered cAMP-bound structural conformation
H620Q
additional information
H620Q
-
the mutant shows reduced PDE6 activity that may result in an increased Ca2+ to promote photoreceptor death
H620Q
-
generation of Pde6bH620Q mice as mouse model, knockdown of guanylate cyclase and cGMP-gated Na+/Ca2+ channels, phenotype compared to control C57BL/6J mice, overview
additional information
-
overexpression of PDE6 gamma subunit in rod photoreceptors decreases the rate of rise of the rod response at dim intensities and also produces a marked acceleration in the falling phase of the light response and more rapid recovery of sensitivity and circulating current after prolonged light exposure
additional information
-
introduction of a modified Pde6g gene for PDE6gamma into a line of Pde6gtm1/Pde6gtm1 mice that do not express PDE6gamma. The resulting ILE86TER mutant mice have a PDE6gamma that lacks the two final carboxyl-terminal Ile86 and Ile87 residues, a mutation that reduces inhibition by PDE6gamma. ILE86TER rods show a decreased sensitivity and rate of activation, and a decreased rate of decay of the photoresponse, consistent with decreased inhibition of PDE6 alpha and beta by PDE6gamma. ILE86TER mutant rods have a higher rate of spontaneous activation of PDE6 than wild-type rods
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Mono Q, gel filtration, partially purified from N18TG2 and NG108-15 neuroblastoma cells
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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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the expression levels of PDE5 mRNA in the tail artery are significantly decreased in orchidectomized male mice to 31.8% of the levels in sham-operated male mice
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
estrogen withdrawal, but not testosterone withdrawal, is a risk factor for PDE5 inhibitor-induced flushing
medicine
-
treatment of mice with vardenafil (5 mg/kg daily for 4 weeks) decreases high density lipoprotein serum levels and the number of antral follicles as well as induces lesser lipid content in luteal cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Giorgi, M.; Caniglia, C.; Scarsella, G.; Augusti-Tocco, G.
Characterization of 3':5' cyclic nucleotide phosphodiesterase activities of mouse neuroblastoma N18TG2 cells
FEBS Lett.
324
76-80
1993
Mus musculus
Giorgi, M.; Girodano, D.; Caniglia, C.; Biagioni, S.; Augusti-Tocco, G.
Induction of cyclic AMP and cyclic GMP 3:5-cyclic nucleotide phosphodiesterase activities in neuroblastoma lines under differentiating conditions
Int. J. Dev. Neurosci.
15
309-319
1997
Mus musculus
Giordano, D.; De Stefano, M.E.; Citro, G.; Modica, A.; Giorgi, M.
Expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in mouse tissues and cell lines using an antibody against the enzyme amino-terminal domain
Biochim. Biophys. Acta
1539
16-27
2001
Mus musculus
van Staveren, W.C.; Glick, J.; Markerink-van Ittersum, M.; Shimizu, M.; Beavo, J.A.; Steinbusch, H.W.; de Vente, J.
Cloning and localization of the cGMP-specific phosphodiesterase type 9 in the rat brain
J. Neurocytol.
31
729-741
2002
Mus musculus (O70628), Mus musculus, Rattus norvegicus (Q8QZV1)
Wunder, F.; Tersteegen, A.; Rebmann, A.; Erb, C.; Fahrig, T.; Hendrix, M.
Characterization of the first potent and selective PDE9 inhibitor using a cGMP reporter cell line
Mol. Pharmacol.
68
1775-1781
2005
Homo sapiens, Mus musculus (O70628), Mus musculus
Bender, A.T.; Beavo, J.A.
Specific localized expression of cGMP PDEs in Purkinje neurons and macrophages
Neurochem. Int.
45
853-857
2004
Mus musculus
Tsang, S.H.; Woodruff, M.L.; Chen, C.K.; Yamashita, C.Y.; Cilluffo, M.C.; Rao, A.L.; Farber, D.B.; Fain, G.L.
GAP-independent termination of photoreceptor light response by excess gamma subunit of the cGMP-phosphodiesterase
J. Neurosci.
26
4472-4480
2006
Mus musculus
Guo, L.W.; Ruoho, A.E.
The retinal cGMP phosphodiesterase gamma-subunit - a chameleon
Curr. Protein Pept. Sci.
9
611-625
2008
Mus musculus
Wang, S.; Ning, G.; Chen, X.; Yang, J.; Ouyang, H.; Zhang, H.; Tai, P.; Mu, X.; Zhou, B.; Zhang, M.; Xia, G.
PDE5 modulates oocyte spontaneous maturation via cGMP-cAMP but not cGMP-PKG signaling
Front. Biosci.
13
7087-7095
2008
Mus musculus
Davis, R.J.; Tosi, J.; Janisch, K.M.; Kasanuki, J.M.; Wang, N.K.; Kong, J.; Tsui, I.; Cilluffo, M.; Woodruff, M.L.; Fain, G.L.; Lin, C.S.; Tsang, S.H.
Functional rescue of degenerating photoreceptors in mice homozygous for a hypomorphic cGMP phosphodiesterase 6 b allele (Pde6bH620Q)
Invest. Ophthalmol. Vis. Sci.
49
5067-5076
2008
Mus musculus
Heikaus, C.C.; Stout, J.R.; Sekharan, M.R.; Eakin, C.M.; Rajagopal, P.; Brzovic, P.S.; Beavo, J.A.; Klevit, R.E.
Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: insights into nucleotide specificity, dimerization, and cGMP-dependent conformational change
J. Biol. Chem.
283
22749-22759
2008
Mus musculus (Q8CG03)
Sejima, H.; Tominaga, K.; Egawa, T.; Ikeda, M.; Shibuya, K.; Kameyama, N.; Yamauchi, A.; Shuto, H.; Kataoka, Y.
Gender differences in tail-skin flushing induced by nitrates and phosphodiesterase type 5 inhibitors in a climacteric mouse model
Eur. J. Pharmacol.
624
66-70
2009
Mus musculus
Das, A.; Xi, L.; Kukreja, R.C.
Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta
J. Biol. Chem.
283
29572-29585
2008
Mus musculus
Donato, M.A.; Saraiva, K.L.; Soares e Silva, A.K.; Wanderley, M.I.; Peixoto, C.A.
Follicle development and luteal cell morphology altered by phosphodiesterase-5 inhibitor
Micron
40
845-850
2009
Mus musculus
Tsang, S.H.; Woodruff, M.L.; Lin, C.S.; Jacobson, B.D.; Naumann, M.C.; Hsu, C.W.; Davis, R.J.; Cilluffo, M.C.; Chen, J.; Fain, G.L.
Effect of the ILE86TER mutation in the gamma subunit of cGMP phosphodiesterase (PDE6) on rod photoreceptor signaling
Cell. Signal.
24
181-188
2011
Mus musculus
Tosi, J.; Davis, R.J.; Wang, N.K.; Naumann, M.; Lin, C.S.; Tsang, S.H.
shRNA knockdown of guanylate cyclase 2e or cyclic nucleotide gated channel alpha 1 increases photoreceptor survival in a cGMP phosphodiesterase mouse model of retinitis pigmentosa
J. Cell. Mol. Med.
15
1778-1787
2011
Mus musculus, Mus musculus C57/BL6J
Chu, U.B.; Song, J.; Mavlyutov, T.A.; Guo, L.W.
In vitro interaction of tubulin with the photoreceptor cGMP phosphodiesterase gamma-subunit
Neurosci. Lett.
482
225-229
2010
Bos taurus, Mus musculus
Kelly, M.P.; Adamowicz, W.; Bove, S.; Hartman, A.J.; Mariga, A.; Pathak, G.; Reinhart, V.; Romegialli, A.; Kleiman, R.J.
Select 3,5-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain
Cell. Signal.
26
383-397
2014
Mus musculus, Rattus norvegicus
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