High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A

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. Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling. Protects against cell death induced by hydrogen peroxide and staurosporine.

Classification

Family (Pfam)

PF00989 PAS, PF08629 PDE8, PF28324 PDE8_3rd, PF23198 PDE8A_N, PF00233 PDEase_I

InterPro

HD/PDEase_dom, PAS, PAS-like_dom_sf, PAS_fold, PDE8-like_REC_N, PDEase, PDEase_catalytic_dom, PDEase_catalytic_dom_sf, PDEase_CS

Functional cluster

Protein Serine/Threonine Kinases

Experimental structures · PDB · 10

• 3ECM X-ray 1.90A
• 3ECN X-ray 2.10A
• 7CWA X-ray 2.80A
• 7CWF X-ray 2.80A
• 7CWG X-ray 2.80A
• 7VSL X-ray 2.50A
• 7VTV X-ray 2.80A
• 7VTW X-ray 2.80A
• 7VTX X-ray 2.50A
• 8YTA X-ray 2.50A

A predicted model is available from AlphaFold.

Gene Ontology · 13

• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
• GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
• GO:0019900 kinase binding
• GO:0046872 metal ion binding
• GO:0030295 protein kinase activator activity
• GO:0006198 cAMP catabolic process
• GO:0071364 cellular response to epidermal growth factor stimulus
• GO:0141162 negative regulation of cAMP/PKA signal transduction
• GO:0070374 positive regulation of ERK1 and ERK2 cascade
• GO:0006355 regulation of DNA-templated transcription
• GO:0007165 signal transduction

Drugs targeting this protein · 3

• FLAVOXATE HYDROCHLORIDE inhibitor
• PENTOXIFYLLINE inhibitor
• DIPYRIDAMOLE inhibitor

Related proteins · sequence + function similarity

• High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A 0.96
• High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B 0.92
• High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B 0.91
• High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8 0.79
• Probable 3',5'-cyclic phosphodiesterase pde-1 0.77
• High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A 0.76
• High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A 0.76
• Probable 3',5'-cyclic phosphodiesterase pde-6 0.76
• High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A 0.75
• High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A 0.74
• Probable 3',5'-cyclic phosphodiesterase pde-2 0.73
• 3',5'-cyclic-AMP phosphodiesterase 4B 0.71

Co-cited proteins · studied together in the literature

• High affinity 3',5'-cyclic-AMP phosphodiesterase 7A 1 shared papers
• High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A 1 shared papers
• High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8 1 shared papers
• RAF proto-oncogene serine/threonine-protein kinase 1 shared papers

Literature · 13 cited papers

• Phosphodiesterase-8A binds to and regulates Raf-1 kinase. Proc. Natl. Acad. Sci. U.S.A. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation. FEBS Lett. · 2012
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity. Biochemistry · 2008
• Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell · 2008
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Human phosphodiesterase 8A splice variants: cloning, gene organization, and tissue distribution. Gene · 2001
• T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3. Proc. Natl. Acad. Sci. U.S.A. · 2001
• … and 1 more in the literature graph