3',5'-cyclic-AMP phosphodiesterase 4B
Also known as: DPDE4, PDE4B
Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Classification
- Family (Pfam)
- PF18100 PDE4_UCR, PF00233 PDEase_I
- InterPro
- HD/PDEase_dom, PDE4_UCR, PDEase, PDEase_catalytic_dom, PDEase_catalytic_dom_sf, PDEase_CS
- Functional cluster
- Zinc-Finger & Chromatin Regulatory Proteins
Experimental structures · PDB · 42
- 1F0J X-ray 1.77A
- 1RO6 X-ray 2.00A
- 1RO9 X-ray 2.13A
- 1ROR X-ray 2.00A
- 1TB5 X-ray 2.15A
- 1XLX X-ray 2.19A
- 1XLZ X-ray 2.06A
- 1XM4 X-ray 2.31A
- 1XM6 X-ray 1.92A
- 1XMU X-ray 2.30A
- 1XMY X-ray 2.40A
- 1XN0 X-ray 2.31A
- … and 30 more
A predicted model is available from AlphaFold.
Gene Ontology · 31
- GO:0005813 centrosome
- GO:0005829 cytosol
- GO:0043197 dendritic spine
- GO:0060076 excitatory synapse
- GO:0000930 gamma-tubulin complex
- GO:0014069 postsynaptic density
- GO:0008021 synaptic vesicle
- GO:0005891 voltage-gated calcium channel complex
- GO:0030018 Z disc
- GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
- GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
- GO:0005246 calcium channel regulator activity
- GO:0030552 cAMP binding
- GO:0043015 gamma-tubulin binding
- GO:0046872 metal ion binding
- GO:0044325 transmembrane transporter binding
- GO:0006198 cAMP catabolic process
- GO:0071872 cellular response to epinephrine stimulus
- GO:0071222 cellular response to lipopolysaccharide
- GO:0071466 cellular response to xenobiotic stimulus
- GO:0050900 leukocyte migration
- GO:0071878 negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway
- GO:0141162 negative regulation of cAMP/PKA signal transduction
- GO:1901898 negative regulation of relaxation of cardiac muscle
- GO:0030593 neutrophil chemotaxis
- GO:0001780 neutrophil homeostasis
- GO:0032743 positive regulation of interleukin-2 production
- GO:0032729 positive regulation of type II interferon production
- GO:1902514 regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
- GO:0086004 regulation of cardiac muscle cell contraction
- GO:0050852 T cell receptor signaling pathway
Drugs targeting this protein · 28
- AMLEXANOX inhibitor
- OXTRIPHYLLINE inhibitor
- THEOPHYLLINE SODIUM GLYCINATE inhibitor
- FLAVOXATE HYDROCHLORIDE inhibitor
- THEOPHYLLINE inhibitor
- AMINOPHYLLINE inhibitor
- DYPHYLLINE inhibitor
- ROFLUMILAST inhibitor
- IBUDILAST inhibitor
- TOFIMILAST inhibitor
- TRANIMILAST inhibitor
- TETOMILAST inhibitor
- LOTAMILAST inhibitor
- DIFAMILAST inhibitor
- HT-0712 inhibitor
- DOVRAMILAST inhibitor
- OGLEMILAST inhibitor
- REVAMILAST inhibitor
- ENSIFENTRINE inhibitor
- CRISABOROLE inhibitor
- MK-0873 inhibitor
- CILOMILAST inhibitor
- APREMILAST inhibitor
- DROTAVERINE inhibitor
- GSK-256066 inhibitor
- PENTOXIFYLLINE inhibitor
- ROLIPRAM inhibitor
- DIPYRIDAMOLE inhibitor
Related proteins · sequence + function similarity
- 3',5'-cyclic-AMP phosphodiesterase 4B 0.99
- 3',5'-cyclic-AMP phosphodiesterase 4D 0.97
- 3',5'-cyclic-AMP phosphodiesterase 4D 0.94
- 3',5'-cyclic-AMP phosphodiesterase 4D 0.93
- 3',5'-cyclic-AMP phosphodiesterase 4C 0.83
- 3',5'-cyclic-AMP phosphodiesterase, isoform F 0.82
- 3',5'-cyclic-AMP phosphodiesterase 4A 0.82
- 3',5'-cyclic-AMP phosphodiesterase 4A 0.81
- 3',5'-cyclic-AMP phosphodiesterase 4C 0.80
- 3',5'-cyclic-AMP phosphodiesterase 4A 0.80
- 3',5'-cyclic-AMP phosphodiesterase 4C 0.79
- Probable 3',5'-cyclic-AMP phosphodiesterase pde-4 0.78
Co-cited proteins · studied together in the literature
- 3',5'-cyclic-AMP phosphodiesterase 4D 7 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4B 1 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4C 2 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4A 2 shared papers
- cGMP-specific 3',5'-cyclic phosphodiesterase 1 shared papers
- Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B 1 shared papers
- Disrupted in schizophrenia 1 protein 1 shared papers
Literature · 15 cited papers
- Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors. Bioorg. Med. Chem. Lett. · 2008
- Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem. J. · 2007
- PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 variant whose isoform-specifying N-terminal region is identical to that of cAMP phosphodiesterase-4D6 (PDE4D6). J. Pharmacol. Exp. Ther. · 2007
- The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
- A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat. Biotechnol. · 2005
- Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure · 2004
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol. Cell · 2004
- Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J. Mol. Biol. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. Science · 2000
- Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3. Biochem. J. · 1997
- … and 3 more in the literature graph
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