Phosphodiesterase 4D, cAMP Specific (PDE4D)

DPDE3; PDE43; Dunce(Drosophila)Homolog Phosphodiesterase E3; cAMP-specific 3',5'-cyclic phosphodiesterase 4D

SPN	Q094
HGNC	8783
MGI	99555
PubMed	19426955
RGD	3281
UniProt	Q08499
Wiki	PDE4D

PDE4D encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.The protein structures of these variants conform to that of other PDE4D isoforms, with a variable N-terminus containing UCR1 and UCR2, followed by a C-terminal catalytic core.Cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. PDE4D is a class IV cAMP-specific PDE. The PDE4D gene is complex, with at least 9 different variants encoding functional proteins.

Reference

"A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs."
Mol. Cell. Biol. 13:6558-6571(1993) [PubMed] [Europe PMC] [Abstract]

"Identification of cyclic AMP-phosphodiesterase variants from the PDE4D gene expressed in human peripheral mononuclear cells."
FEBS Lett. 384:97-102(1996) [PubMed] [Europe PMC] [Abstract]

"Isolation of a cDNA encoding a human rolipram-sensitive cyclic AMP phosphodiesterase (PDE IVD)."
Gene 138:253-256(1994) [PubMed] [Europe PMC] [Abstract]

"Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene."
Biochem. J. 328:539-548(1997) [PubMed] [Europe PMC] [Abstract]

"Phosphodiesterases 4D and 7A splice variants in the response of HUVEC cells to TNF-alpha1."
Biochem. Biophys. Res. Commun. 274:415-421(2000) [PubMed] [Europe PMC] [Abstract]

"Cloning and characterization of novel PDE4D isoforms PDE4D6 and PDE4D7."
Cell. Signal. 15:883-891(2003) [PubMed] [Europe PMC] [Abstract]

"The gene encoding phosphodiesterase 4D confers risk of ischemic stroke."
Nat. Genet. 35:131-138(2003) [PubMed] [Europe PMC] [Abstract]

Erratum
Nat. Genet. 37:555-555(2005)

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Delineation of RAID1, the RACK1 interaction domain located within the unique N-terminal region of the cAMP-specific phosphodiesterase, PDE4D5."
BMC Biochem. 3:24-24(2002) [PubMed] [Europe PMC] [Abstract]

"The unique amino-terminal region of the PDE4D5 cAMP phosphodiesterase isoform confers preferential interaction with beta-arrestins."
J. Biol. Chem. 278:49230-49238(2003) [PubMed] [Europe PMC] [Abstract]

"The oligomerization state determines regulatory properties and inhibitor sensitivity of type 4 cAMP-specific phosphodiesterases."
J. Biol. Chem. 279:30338-30348(2004) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"Many hypotheses but no replication for the association between PDE4D and stroke."
Nat. Genet. 38:1091-1092(2006) [PubMed] [Europe PMC] [Abstract]

"Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors."
J. Biol. Chem. 282:10414-10422(2007) [PubMed] [Europe PMC] [Abstract]

"Phosphoproteome of resting human platelets."
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK."
Biochem. J. 428:55-65(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of phosphodiesterase 4D and inhibitor complex."
FEBS Lett. 530:53-58(2002) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of AMP-bound PDE4 suggests a mechanism for phosphodiesterase catalysis."
Biochemistry 42:13220-13226(2003) [PubMed] [Europe PMC] [Abstract]

"Three-dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity."
Structure 11:865-873(2003) [PubMed] [Europe PMC] [Abstract]

"Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine suggest a conformation determinant of inhibitor selectivity."
J. Biol. Chem. 279:13095-13101(2004) [PubMed] [Europe PMC] [Abstract]

"Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram."
J. Mol. Biol. 337:355-365(2004) [PubMed] [Europe PMC] [Abstract]

"A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases."
Mol. Cell 15:279-286(2004) [PubMed] [Europe PMC] [Abstract]

"Structural basis for the activity of drugs that inhibit phosphodiesterases."
Structure 12:2233-2247(2004) [PubMed] [Europe PMC] [Abstract]

"A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design."
Nat. Biotechnol. 23:201-207(2005) [PubMed] [Europe PMC] [Abstract]

"Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase."
J. Med. Chem. 49:1867-1873(2006) [PubMed] [Europe PMC] [Abstract]

"Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors."
Biochem. J. 408:193-201(2007) [PubMed] [Europe PMC] [Abstract]

"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. 19:2612-2624(2007) [PubMed] [Europe PMC] [Abstract]

"The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10."
J. Mol. Biol. 371:302-307(2007) [PubMed] [Europe PMC] [Abstract]

"Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis."
Am. J. Hum. Genet. 90:740-745(2012) [PubMed] [Europe PMC] [Abstract]

"Exome sequencing identifies PDE4D mutations in acrodysostosis."
Am. J. Hum. Genet. 90:746-751(2012) [PubMed] [Europe PMC] [Abstract]

"PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct syndromes with or without GPCR-signaling hormone resistance."
J. Clin. Endocrinol. Metab. 97:E2328-E2338(2012) [PubMed] [Europe PMC] [Abstract]

"Identification of novel mutations confirms Pde4d as a major gene causing acrodysostosis."
Hum. Mutat. 34:97-102(2013) [PubMed] [Europe PMC] [Abstract]