Descriptions

PDE4D encodes a cAMP-specific 3',5'-cyclic phosphodiesterase 4D involved in the hydrolysis of cAMP and cGMP, which play important roles in many physiological processes. The autoinhibitory domain of PDE4D is located in the upstream conserved region 2 (UCR2) that inhibits PDE4D activity. Specifically, the α-helical NQVSE[F/Y]ISXTFLD sequence within UCR2 can fold across the catalytic pocket and thus control access to it. In addition, UCR1 can interact with UCR2 to regulate the activity of PDE4.

Autoinhibitory domains (AIDs)

Target domain

343-672 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)

Relief mechanism

PTM

Assay

Target domain

343-672 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

2 structures for P54748

Entry ID Method Resolution Chain Position Source
1LOI NMR - A 1-25 PDB
AF-P54748-F1 Predicted AlphaFoldDB

No variants for P54748

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P54748

No associated diseases with P54748

4 regional properties for P54748

Type Name Position InterPro Accession
domain Ras-like guanine nucleotide exchange factor, N-terminal 49 - 175 IPR000651
domain Ras guanine-nucleotide exchange factors catalytic domain 197 - 433 IPR001895
domain EF-hand domain 466 - 501 IPR002048
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 540 - 597 IPR002219

Functions

Description
EC Number 3.1.4.53 Phosphoric diester hydrolases
Subcellular Localization
  • [Isoform 2]: Cytoplasm, cytosol
  • Membrane; Peripheral membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

6 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
Schaffer collateral - CA1 synapse A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell.

4 GO annotations of molecular function

Name Definition
3',5'-cyclic-AMP phosphodiesterase activity Catalysis of the reaction
3',5'-cyclic-GMP phosphodiesterase activity Catalysis of the reaction
cAMP binding Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
metal ion binding Binding to a metal ion.

8 GO annotations of biological process

Name Definition
cAMP catabolic process The chemical reactions and pathways resulting in the breakdown of the nucleotide cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate).
cAMP-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via cyclic AMP (cAMP). Includes production of cAMP, and downstream effectors that further transmit the signal within the cell.
cellular response to xenobiotic stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
modulation of chemical synaptic transmission Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission.
regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway Any process that modulates the frequency, rate or extent of an adenylate cyclase-activating G protein-coupled receptor signaling pathway.
regulation of protein kinase A signaling Any process that modulates the rate, frequency, or extent of protein kinase A signaling. PKA signaling is the series of reactions, mediated by the intracellular serine/threonine kinase protein kinase A, which occurs as a result of a single trigger reaction or compound.
response to xenobiotic stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
sensory perception of smell The series of events required for an organism to receive an olfactory stimulus, convert it to a molecular signal, and recognize and characterize the signal. Olfaction involves the detection of chemical composition of an organism's ambient medium by chemoreceptors. This is a neurological process.

32 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q28156 PDE5A cGMP-specific 3',5'-cyclic phosphodiesterase Bos taurus (Bovine) SS
P23439 PDE6B Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Bos taurus (Bovine) PR
P52731 PDE6C Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' Gallus gallus (Chicken) PR
H2QL32 PDE9A High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Pan troglodytes (Chimpanzee) PR
Q9VJ79 Pde11 Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11 Drosophila melanogaster (Fruit fly) SS
Q9W4T4 dnc 3',5'-cyclic-AMP phosphodiesterase, isoform I Drosophila melanogaster (Fruit fly) SS
Q9HCR9 PDE11A Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A Homo sapiens (Human) SS
O76083 PDE9A High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Homo sapiens (Human) PR
Q07343 PDE4B cAMP-specific 3',5'-cyclic phosphodiesterase 4B Homo sapiens (Human) EV SS
Q08499 PDE4D cAMP-specific 3',5'-cyclic phosphodiesterase 4D Homo sapiens (Human) EV
O76074 PDE5A cGMP-specific 3',5'-cyclic phosphodiesterase Homo sapiens (Human) EV
Q08493 PDE4C cAMP-specific 3',5'-cyclic phosphodiesterase 4C Homo sapiens (Human) EV SS
P51160 PDE6C Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' Homo sapiens (Human) PR
P35913 PDE6B Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Homo sapiens (Human) PR
Q9Y233 PDE10A cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Homo sapiens (Human) PR
P27815 PDE4A cAMP-specific 3',5'-cyclic phosphodiesterase 4A Homo sapiens (Human) EV SS
P23440 Pde6b Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Mus musculus (Mouse) PR
O70628 Pde9a High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Mus musculus (Mouse) PR
Q8CG03 Pde5a cGMP-specific 3',5'-cyclic phosphodiesterase Mus musculus (Mouse) SS
Q8CA95 Pde10a cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Mus musculus (Mouse) PR
P0C1Q2 Pde11a Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A Mus musculus (Mouse) SS
Q3UEI1 Pde4c cAMP-specific 3',5'-cyclic phosphodiesterase 4C Mus musculus (Mouse) PR
Q01063 Pde4d 3',5'-cyclic-AMP phosphodiesterase 4D Mus musculus (Mouse) SS
O89084 Pde4a 3',5'-cyclic-AMP phosphodiesterase 4A Mus musculus (Mouse) SS
P14646 Pde4b cAMP-specific 3',5'-cyclic phosphodiesterase 4B Rattus norvegicus (Rat) SS
P14270 Pde4d cAMP-specific 3',5'-cyclic phosphodiesterase 4D Rattus norvegicus (Rat) PR
Q8QZV1 Pde9a High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Rattus norvegicus (Rat) PR
Q9QYJ6 Pde10a cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Rattus norvegicus (Rat) PR
Q8VID6 Pde11a Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A Rattus norvegicus (Rat) SS
O54735 Pde5a cGMP-specific 3',5'-cyclic phosphodiesterase Rattus norvegicus (Rat) SS
P14644 Pde4c cAMP-specific 3',5'-cyclic phosphodiesterase 4C Rattus norvegicus (Rat) PR
Q22000 pde-4 Probable 3',5'-cyclic phosphodiesterase pde-4 Caenorhabditis elegans PR
10 20 30 40 50 60
MEPPAAPSER SLSLSLPGPR EGQATLKPPP QHLWRQPRTP IRIQQRGYPD SAERSETERS
70 80 90 100 110 120
PHRPIERADA VDTGDRPGLR TTRMSWPSSF HGTGTGGGSS RRLEAENGPT PSPGRSPLDS
130 140 150 160 170 180
QASPGLVLHA GATTSQRRES FLYRSDSDYD MSPKAVSRSS SVASEAHAED LIVTPFAQVL
190 200 210 220 230 240
ASLRSVRSNF SLLTNVPIPS NKRSPLGGPP SVCKATLSEE TCQQLARETL EELDWCLEQL
250 260 270 280 290 300
ETMQTYRSVS EMASHKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ NEVEIPSPTP
310 320 330 340 350 360
RQRAFQQPPP SVLRQSQPMS QITGLKKLVH TGSLNTNVPR FGVKTDQEDL LAQELENLSK
370 380 390 400 410 420
WGLNIFCVSE YAGGRSLSCI MYTIFQERDL LKKFHIPVDT MMMYMLTLED HYHADVAYHN
430 440 450 460 470 480
SLHAADVLQS THVLLATPAL DAVFTDLEIL AALFAAAIHD VDHPGVSNQF LINTNSELAL
490 500 510 520 530 540
MYNDESVLEN HHLAVGFKLL QEENCDIFQN LSKRQRQSLR KMVIDMVLAT DMSKHMTLLA
550 560 570 580 590 600
DLKTMVETKK VTSSGVLLLD NYSDRIQVLR NMVHCADLSN PTKPLELYRQ WTDRIMAEFF
610 620 630 640 650 660
QQGDRERERG MEISPMCDKH TASVEKSQVG FIDYIVHPLW ETWADLVHPD AQDILDTLED
670 680 690 700 710 720
NRDWYHSAIR QSPSPPLEEE PGGLGHPSLP DKFQFELTLE EEEEEDSLEV PGLPTTEETF
730 740 750 760 770 780
LAAEDARAQA VDWSKVKGPS TTVVEVAERL KQETASAYGA PQESMEAVGC SFSPGTPILP
790 800 810 820 830 840
DVRTLSSSEE APGLLGLPST AAEVEAPRDH LAATRACSAC SGTSGDNSAI ISAPGRWGSG
GDPA