3',5'-cyclic-AMP phosphodiesterase 4D
Also known as: DPDE3, PDE4D
Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Classification
- Family (Pfam)
- PF18100 PDE4_UCR, PF00233 PDEase_I
- InterPro
- PDE4_UCR, PDEase, PDEase_catalytic_dom, PDEase_catalytic_dom_sf, PDEase_CS
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 118
- 1E9K NMR
- 1MKD X-ray 2.90A
- 1OYN X-ray 2.00A
- 1PTW X-ray 2.30A
- 1Q9M X-ray 2.30A
- 1TB7 X-ray 1.63A
- 1TBB X-ray 1.60A
- 1XOM X-ray 1.55A
- 1XON X-ray 1.72A
- 1XOQ X-ray 1.83A
- 1XOR X-ray 1.54A
- 1Y2B X-ray 1.40A
- … and 106 more
A predicted model is available from AlphaFold.
Gene Ontology · 39
- GO:0016324 apical plasma membrane
- GO:0034704 calcium channel complex
- GO:0005813 centrosome
- GO:0005829 cytosol
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0005891 voltage-gated calcium channel complex
- GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
- GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
- GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
- GO:0051117 ATPase binding
- GO:0031698 beta-2 adrenergic receptor binding
- GO:0005246 calcium channel regulator activity
- GO:0030552 cAMP binding
- GO:0019899 enzyme binding
- GO:1901363 heterocyclic compound binding
- GO:0046872 metal ion binding
- GO:0097110 scaffold protein binding
- GO:0030545 signaling receptor regulator activity
- GO:0044325 transmembrane transporter binding
- GO:0071875 adrenergic receptor signaling pathway
- GO:0006198 cAMP catabolic process
- GO:0071320 cellular response to cAMP
- GO:0071872 cellular response to epinephrine stimulus
- GO:0061028 establishment of endothelial barrier
- GO:0106072 negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0141162 negative regulation of cAMP/PKA signal transduction
- GO:0045822 negative regulation of heart contraction
- GO:1901898 negative regulation of relaxation of cardiac muscle
- GO:0010460 positive regulation of heart rate
- GO:0032743 positive regulation of interleukin-2 production
- GO:0032754 positive regulation of interleukin-5 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:1901844 regulation of cell communication by electrical coupling involved in cardiac conduction
- GO:0002027 regulation of heart rate
- GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
- GO:0050852 T cell receptor signaling pathway
Disease associations
- acrodysostosis 2 with or without hormone resistance MONDO:0013822
Drugs targeting this protein · 29
- 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
- ZATOLMILAST 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 4D 1.00
- 3',5'-cyclic-AMP phosphodiesterase 4D 0.93
- 3',5'-cyclic-AMP phosphodiesterase 4B 0.93
- 3',5'-cyclic-AMP phosphodiesterase 4B 0.93
- 3',5'-cyclic-AMP phosphodiesterase 4A 0.89
- 3',5'-cyclic-AMP phosphodiesterase 4A 0.85
- 3',5'-cyclic-AMP phosphodiesterase 4C 0.85
- 3',5'-cyclic-AMP phosphodiesterase 4A 0.82
- 3',5'-cyclic-AMP phosphodiesterase, isoform F 0.80
- 3',5'-cyclic-AMP phosphodiesterase 4C 0.79
- 3',5'-cyclic-AMP phosphodiesterase 4C 0.77
- Probable 3',5'-cyclic-AMP phosphodiesterase pde-4 0.76
Co-cited proteins · studied together in the literature
- 3',5'-cyclic-AMP phosphodiesterase 4B 7 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4A 3 shared papers
- cAMP-dependent protein kinase type I-alpha regulatory subunit 3 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4C 2 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4D 2 shared papers
- Secernin-3 1 shared papers
- Zinc finger protein 783 1 shared papers
- 3',5'-cyclic-AMP phosphodiesterase 4D 2 shared papers
- Beta-arrestin-2 1 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 · 37 cited papers
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct syndromes with or without GPCR-signaling hormone resistance. J. Clin. Endocrinol. Metab. · 2012
- Identification of novel mutations confirms Pde4d as a major gene causing acrodysostosis. Hum. Mutat. · 2013
- Exome sequencing identifies PDE4D mutations in acrodysostosis. Am. J. Hum. Genet. · 2012
- Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am. J. Hum. Genet. · 2012
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK. Biochem. J. · 2010
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
- Phosphoproteome of resting human platelets. J. Proteome Res. · 2008
- 1H NMR structural and functional characterisation of a cAMP-specific phosphodiesterase-4D5 (PDE4D5) N-terminal region peptide that disrupts PDE4D5 interaction with the signalling scaffold proteins, beta-arrestin and RACK1. Cell. Signal. · 2007
- Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem. J. · 2007
- … and 25 more in the literature graph
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