a cAMP-responsive region, a number of GC-rich regions, and binding sites for SP1, AP1 and AP2
MAPPING
cloned
Y
linked
N
status
confirmed
RNA
TRANSCRIPTS
type
messenger
identification
nb exons
type
bp
product
Protein
kDa
AA
specific expression
Year
Pubmed
10
splicing
7801
-
585
-
2003
14517540
also called PDE4D1, isoform 8
11
splicing
7715
-
507
-
2012
22464252
also called PDE4D2, isoform 7
part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9
lack the N-terminal UCR1 domain, which regulates catalytic activity along with UCR2
15
splicing
7783
76.3
673
-
2003
14517540
PDE4D3, isoform 2
found in the cardiac ryanodine receptor (RyR2)/calcium-release-channel complex (required for excitation-contraction coupling in heart muscle)and playing a protective role in the heart against heart failure and arrhythmias
reduced in failing human hearts, contributing to PKA-hyperphosphorylated, "leaky" RyR2 channels that promote cardiac dysfunction and arrhythmias
contains a regulatory domain target for phosphorylation at the amino terminus of the protein and that Ser54 in this domain plays a crucial role in activation (PMID: 8663227)
is responsible for maintaining a microdomain with low cAMP concentration at the centrosome (PMID: 22908311)
15
splicing
8240
-
809
-
2012
22464252
also called PDE4D4
isoform 1
two highly evolutionarily conserved upstream regions (UCR1 and UCR2) and the large catalytic domain
15
splicing
7979
-
745
-
2012
22464252
also called PDE4D5, isoform 4
promoter up-regulated reporter gene expression in response to increased cell cAMP
binding to GNB2L1 via its unique N-terminus
interaction of PDE4D5 with both the N- and C-domains of ARRB2 are essential for beta2-AR (ADRB2) regulation (PMID: 17288540)
can be sumoylated (PMID: 20196770)
two highly evolutionarily conserved upstream regions (UCR1 and UCR2) and the large catalytic domain
TRPV1 association with ARRB2 is critical to receptor desensitization via its ability to scaffold the phosphodiesterase PDE4D5 to the receptor, regulating TRPV1 phosphorylation (PMID: 23360390)
RACK1 and ARRB2 inhibit the dimerization of PDE4D5 (PMID: 26257302)
10
splicing
7591
59.1
518
only in brain
2012
22464252
also called PDE4D6, isoform 9
lack the N-terminal UCR1 domain, which regulates catalytic activity along with UCR2
17
splicing
8130
84.7
748
-
2012
22464252
PDE4D7, isoform 3
two highly evolutionarily conserved upstream regions (UCR1 and UCR2) and the large catalytic domain
15
splicing
7757
77.7
687
heart, muscle, lung
2003
12834813
also called PDE4D8, isoform 5
ADRB1 associates with PDE4D8 through the receptor C-terminal PDZ motif-dependent binding to synaptic-associated protein 97 (DLG1)
14
splicing
8395
76.8
679
-
2003
14517540
also called PDE4D9, isoform 6
mitotic activation of the DISC1-inducible cyclic PDE4D9, through multi-site phosphorylation, influences cell cycle progression (PMID: 24815749)
associated with the cytoskeleton and the centrosome
basic FUNCTION
cAMP specific nucleotide phosphodiesterase may be involved in signal transduction
playing a pivotal role in the regulation of airway smooth muscle relaxation by catalyzing the hydrolysis of cAMP
plays a critical role in the memory and hippocampal neurogenesis mediated by cAMP signaling
regulating the levels of cAMP in the cell
regulator of airway smooth-muscle contractility
cyclic nucleotide PDEs play important role in the achievement of meiotic competency by reducing intraoocyte cyclic nucleotides level in mammalian oocytes
role of PDE4D in BRAF-mutated melanoma as regulator of cell invasion
CELLULAR PROCESS
PHYSIOLOGICAL PROCESS
PATHWAY
metabolism
nucleic
signaling
signal transduction
cyclic nucleotide metabolism
a component
homodimer for the long isoforms
monomeric for isoforms with truncated N-termini
INTERACTION
DNA
RNA
small molecule
metal binding,
two divalent metal cations per subunit :
Zn2+ (preferentially in site 1)
Mg2+ and/or Mn2+ (preferentially in site 2)
protein
RYR2 channel
upregulation of NOX4 leads to an upregulation of PDE4A, PDE4B, and PDE4D and increased hydrolysis of cAMP which in turn augments cell replication and angiogenesis
PRKACA and PDE4D anchoring to AKAP9 provides distinct regulation of cAMP signals at the centrosome
CC2D1A is a novel regulator of PDE4D
PDE4D interacts directly with Neuropilins, positive regulators of HH pathway