3',5'-cyclic-nucleotide Phosphodiesterase
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3',5'-cyclic-nucleotide Phosphodiesterase
3′,5′-cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a protein family, family of phosphodiesterases. Generally, these enzymes hydrolyze a nucleoside 3′,5′-cyclic phosphate to a nucleoside 5′-phosphate: :nucleoside 3′,5′-cyclic phosphate + H2O = nucleoside 5′-phosphate They thus control the cellular levels of the cyclic second messengers and the rates of their degradation. Some examples of nucleoside 3′,5′-cyclic phosphate include: *Cyclic adenosine monophosphate, 3′,5′-cyclic AMP *3′,5′-cyclic dAMP *3′,5′-cyclic IMP *Cyclic guanosine monophosphate, 3′,5′-cyclic GMP *3′,5′-cyclic CMP There are 11 distinct phosphodiesterase families (PDE1–PDE11) with a variety in isoforms and splicing having unique three-dimensional structure, kinetic properties, modes of regulation, intracellular localization, cellular expression, and inhibitor sensitivities. Nomenclature The systematic name for this enzyme is 3′,5′-cyclic-nucleotide 5'- ...
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Protein Family
A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be confused with family as it is used in taxonomy. Proteins in a family descend from a common ancestor and typically have similar three-dimensional structures, functions, and significant sequence similarity. Sequence similarity (usually amino-acid sequence) is one of the most common indicators of homology, or common evolutionary ancestry. Some frameworks for evaluating the significance of similarity between sequences use sequence alignment methods. Proteins that do not share a common ancestor are unlikely to show statistically significant sequence similarity, making sequence alignment a powerful tool for identifying the members of protein families. Families are sometimes grouped together into larger clades called superfamilies based on st ...
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PDE10A2
Phosphodiesterase 1, PDE1, EC 3.1.4.1, systematic name oligonucleotide 5-nucleotidohydrolase) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase. It is one of the 11 families of phosphodiesterase (PDE1-PDE11). Phosphodiesterase 1 has three subtypes, PDE1A, PDE1B and PDE1C which divide further into various isoforms. The various isoforms exhibit different affinities for cAMP and cGMP. Discovery The existence of the Ca2+-stimulated Phosphodiesterase 1 was first demonstrated by Cheung (1970), Kakiuchi and Yamazaki (1970) as a result of their research on bovine brain and rat brain respectively. It has since been found to be widely distributed in various mammalian tissues as well as in other eukaryotes. It is now one of the most intensively studied member of the PDE superfamily of enzymes, which today represents 11 gene families, and the best characterized one as well. Further research in the field along with increased availability of mono ...
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PDE10A
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the ''PDE10A'' gene. Various cellular responses are regulated by the second messengers cyclic adenosine monophosphate, cAMP and cyclic guanosine monophosphate, cGMP. Phosphodiesterases, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate. Inhibitors * AMG-579 * Balipodect (TAK-063): IC50 = 300 pM * Compound 96: IC50 = 700 pM, high selectivity against all other members of the PDE family * CPL500036 * Mardepodect (PF-2545920) * MK-8189 * Papaverine * Tofisopam Research Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans. PDE10A is a regulatory protein involved in the signaling of the striatum, a region of the brain important for controlling movement and cognition. Dysfunction of the striatum has been linked to ...
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PDE9A
High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the ''PDE9A'' gene. The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene. Inhibitors * BAY 73-6691 * PF-04447943 See also * Phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many oth ... References Further reading

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PDE8B
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by the ''PDE8B'' gene. Clinical significance PDE8B expression has been linked to higher survival rates for lung adenocarcinoma Adenocarcinoma of the lung is the most common type of lung cancer, and like other forms of lung cancer, it is characterized by distinct cellular and molecular features. It is classified as one of several non-small cell lung cancers (NSCLC), to d ... patients. References Further reading * * * * * * * * * {{gene-5-stub PAS-domain-containing proteins ...
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PDE8A
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A is an enzyme that in humans is encoded by the ''PDE8A'' gene. Work by Sebastiaan Bol et al. showed that 5 different transcript variants and their corresponding isoforms are expressed in human macrophages, and suggests that this protein may be required by HIV-1 The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics. HIV-1 e ... for its replication. References Further reading * * * * * * * * * {{gene-15-stub PAS-domain-containing proteins ...
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PDE7B
PDE7B is a mammalian gene that encodes a 3'5'-cyclic nucleotide phosphodiesterase (PDE) that converts 3'5'-cyclic adenosine monophosphate (cAMP) to 5'AMP as part of cyclic nucleotide signaling pathways.Sasaki, T., Kotera, J., Yuasa, K., and Omori, K. (2000). Identification of human PDE7B, a cAMP-specific phosphodiesterase. Biochem Biophys Res Commun 271, 575-583. There are 21 PDE genes in mammals that are pharmacologically-grouped into 11 families based on their biochemical characteristics and sequence conservation. The PDE7 family is composed of PDEs encoded by two genes, PDE7A and PDE7B. These PDEs are highly specific for cAMP relative to cGMP CGMP is an initialism. It can refer to: *cyclic guanosine monophosphate (cGMP) * current good manufacturing practice (cGMP) *CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol The Internet Group Manag .... References {{Reflist Enzymes ...
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PDE7A
High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A is an enzyme that in humans is encoded by the ''PDE7A'' gene. Mammals possess 21 cyclic nucleotide phosphodiesterase (PDE) genes that are pharmacologically grouped into 11 families. PDE7A is one of two genes in the PDE7 family, the other being PDE7B. The PDE7 family, along with the PDE4 and PDE8 families, are cAMP-specific, showing little to no activity against 3', 5'-cyclic guanosine monophosphate (cGMP CGMP is an initialism. It can refer to: *cyclic guanosine monophosphate (cGMP) * current good manufacturing practice (cGMP) *CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol The Internet Group Manag ...). References Further reading

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PDE6C
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' is an enzyme that in humans is encoded by the ''PDE6C'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei .... References Further reading * * * * * * * * * {{refend External links GeneReviews/NIH/NCBI/UW entry on Achromatopsia OMIM entries on Achromatopsia
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PDE6B
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the ''PDE6B'' gene. PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa or congenital stationary night blindness. Structure PDE6 is a protein complex located on the photoreceptor's outer segment, and plays an important role in the phototransduction cascade. There are two types of photoreceptors: cones and rods. The rod and cone PDE6 complexes have different structures. PDE6β together with PDE6α and two identical inhibitory subunits, PDE6γ, form the rod PDE6 holoenzyme while the cone PDE6 complex only consists of two identical PDE6α' catalytic subunits. PDE6β, one of the catalytic units in rod PDE6, is composed of three domains: two N-terminal GAF domains a ...
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PDE6A
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha is an enzyme that in humans is encoded by the ''PDE6A'' gene. PDE6A encodes the cyclic-GMP (cGMP) specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 holoenzyme is a heterotrimer composed of an alpha, beta, and two gamma subunits. cGMP is an important regulator of rod cell membrane current, and its dynamic concentration is established by phosphodiesterase 6A cGMP hydrolysis and guanylate cyclase cGMP synthesis. Mutations in PDE6A have been identified as one cause of autosomal recessive retinitis pigmentosa Retinitis pigmentosa (RP) is a member of a group of genetic disorders called inherited retinal dystrophy (IRD) that cause loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visua .... References Further reading * * * * * * * * * * * External links GeneReviews/NCBI/NIH/UW e ...
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