Q01063

SS
Gene name
Pde4d
Protein name
3',5'-cyclic-AMP phosphodiesterase 4D
Names
EC 3.1.4.53 , DPDE3 , cAMP-specific phosphodiesterase 4D
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:238871
EC number
3.1.4.53: Phosphoric diester hydrolases
Protein Class

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)

126-184 (Upstream conserved region 1) SS

Target domain

325-654 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)

Relief mechanism

PTM

Assay

209-287 (Upstream conserved region 2) SS

Target domain

325-654 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q01063

Entry ID Method Resolution Chain Position Source
AF-Q01063-F1 Predicted AlphaFoldDB

40 variants for Q01063

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389286275 20 L>M No EVA
rs3404633012 58 Q>H No EVA
rs3389269076 67 N>I No EVA
rs3404938152 112 G>E No EVA
rs3404205951 113 S>P No EVA
rs3389309752 116 I>N No EVA
rs3389318706 121 F>C No EVA
rs3389318728 165 F>Y No EVA
rs3389276554 174 T>I No EVA
rs3412107645 216 A>S No EVA
rs3404939377 262 S>R No EVA
rs3404939390 263 R>G No EVA
rs3404939381 263 R>Q No EVA
rs3389303280 325 V>A No EVA
rs3389300693 367 F>I No EVA
rs3389286225 380 V>E No EVA
rs3389260294 393 H>Q No EVA
rs3404940754 499 Q>* No EVA
rs3389304974 503 K>R No EVA
rs3389309737 511 A>T No EVA
rs3404640214 513 D>A No EVA
rs3403878407 514 M>R No EVA
rs3404416764 546 D>V No EVA
rs3389299928 564 T>P No EVA
rs3389260236 611 V>M No EVA
rs3389297877 636 I>T No EVA
rs3389300742 646 W>L No EVA
rs3389295860 652 P>T No EVA
rs3389260251 680 E>D No EVA
rs3389304984 683 C>Y No EVA
rs3389299971 695 V>L No EVA
rs3389299971 695 V>M No EVA
rs3389314293 705 K>M No EVA
rs3403191024 712 S>L No EVA
rs3389295900 718 P>L No EVA
rs3389297811 731 E>D No EVA
rs260629578 735 P>S No EVA
rs3389299951 739 V>A No EVA
rs3389305150 743 C>Y No EVA
rs3389305230 745 P>S No EVA

No associated diseases with Q01063

15 regional properties for Q01063

Type Name Position InterPro Accession
domain Protein kinase domain 590 - 938 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 591 - 923 IPR001245
conserved_site Tyrosine-protein kinase, receptor class III, conserved site 649 - 662 IPR001824
domain Immunoglobulin subtype 2 49 - 104 IPR003598-1
domain Immunoglobulin subtype 2 224 - 298 IPR003598-2
domain Immunoglobulin subtype 43 - 112 IPR003599-1
domain Immunoglobulin subtype 121 - 205 IPR003599-2
domain Immunoglobulin subtype 218 - 309 IPR003599-3
domain Immunoglobulin subtype 321 - 411 IPR003599-4
domain Immunoglobulin-like domain 212 - 309 IPR007110-1
domain Immunoglobulin-like domain 427 - 508 IPR007110-2
active_site Tyrosine-protein kinase, active site 789 - 801 IPR008266
domain Immunoglobulin-like beta-sandwich domain 220 - 303 IPR013151
binding_site Protein kinase, ATP binding site 596 - 624 IPR017441
domain Tyrosine-protein kinase, catalytic domain 590 - 925 IPR020635

Functions

Description
EC Number 3.1.4.53 Phosphoric diester hydrolases
Subcellular Localization
  • Cytoplasm
  • Membrane
  • Cytoplasm, cytoskeleton
  • Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
  • Apical cell membrane
  • Colocalized with SHANK2 to the apical membrane of colonic crypt cells (By similarity)
  • Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

10 GO annotations of cellular component

Name Definition
apical plasma membrane The region of the plasma membrane located at the apical end of the cell.
calcium channel complex An ion channel complex through which calcium ions pass.
centrosome A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
myofibril The contractile element of skeletal and cardiac muscle; a long, highly organized bundle of actin, myosin, and other proteins that contracts by a sliding filament mechanism.
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.
potassium channel complex An ion channel complex through which potassium ions pass.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.
voltage-gated calcium channel complex A protein complex that forms a transmembrane channel through which calcium ions may pass in response to changes in membrane potential.

11 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
3',5'-cyclic-nucleotide phosphodiesterase activity Catalysis of the reaction
ATPase binding Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP.
beta-2 adrenergic receptor binding Binding to a beta-2 adrenergic receptor.
calcium channel regulator activity Modulates the activity of a calcium channel.
cyclic-nucleotide phosphodiesterase activity Catalysis of the reaction
enzyme binding Binding to an enzyme, a protein with catalytic activity.
metal ion binding Binding to a metal ion.
signaling receptor regulator activity Binds to and modulates the activity of a receptor.
transmembrane transporter binding Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other.

31 GO annotations of biological process

Name Definition
adrenergic receptor signaling pathway A G protein-coupled receptor signaling pathway initiated by a ligand binding to an adrenergic receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process.
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 cAMP 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 cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus.
cellular response to epinephrine 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 an epinephrine stimulus. Epinephrine is a catecholamine that has the formula C9H13NO3; it is secreted by the adrenal medulla to act as a hormone, and released by certain neurons to act as a neurotransmitter active in the central nervous system.
cellular response to follicle-stimulating hormone 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 follicle-stimulating hormone stimulus.
cellular response to lipopolysaccharide 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 lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
establishment of endothelial barrier The establishment of a barrier between endothelial cell layers, such as those in the brain, lung or intestine, to exert specific and selective control over the passage of water and solutes, thus allowing formation and maintenance of compartments that differ in fluid and solute composition.
memory The activities involved in the mental information processing system that receives (registers), modifies, stores, and retrieves informational stimuli. The main stages involved in the formation and retrieval of memory are encoding (processing of received information by acquisition), storage (building a permanent record of received information as a result of consolidation) and retrieval (calling back the stored information and use it in a suitable way to execute a given task).
multicellular organism growth The increase in size or mass of an entire multicellular organism, as opposed to cell growth.
negative regulation of cAMP-mediated signaling Any process which stops, prevents, or reduces the frequency, rate or extent of cAMP-mediated signaling.
negative regulation of heart contraction Any process that stops, prevents, or reduces the frequency, rate or extent of heart contraction.
negative regulation of peptidyl-serine phosphorylation Any process that stops, prevents, or reduces the frequency, rate or extent of the phosphorylation of peptidyl-serine.
negative regulation of relaxation of cardiac muscle Any process that stops, prevents or reduces the frequency, rate or extent of relaxation of cardiac muscle.
neutrophil chemotaxis The directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding.
neutrophil migration The movement of a neutrophil within or between different tissues and organs of the body.
ovulation from ovarian follicle The process leading to the rupture of the follicle, releasing the centrally located oocyte into the oviduct. An example of this is found in Mus musculus.
positive regulation of cell-cell adhesion Any process that activates or increases the rate or extent of cell adhesion to another cell.
positive regulation of heart rate Any process that activates or increases the frequency or rate of heart contraction.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of smooth muscle cell migration Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration.
positive regulation of smooth muscle cell proliferation Any process that activates or increases the rate or extent of smooth muscle cell proliferation.
protein-containing complex assembly The aggregation, arrangement and bonding together of a set of macromolecules to form a protein-containing complex.
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel Any process that modulates the frequency, rate or extent of generation of calcium ion transmembrane transport via high voltage-gated calcium channel.
regulation of cAMP-mediated signaling Any process which modulates the frequency, rate or extent of cAMP-mediated signaling.
regulation of cardiac muscle cell contraction Any process that modulates the frequency, rate or extent of cardiac muscle cell contraction.
regulation of cell communication by electrical coupling involved in cardiac conduction Any process that modulates the frequency, rate or extent of cell communication by electrical coupling involved in cardiac conduction.
regulation of G protein-coupled receptor signaling pathway Any process that modulates the frequency, rate or extent of G protein-coupled receptor signaling pathway.
regulation of heart rate Any process that modulates the frequency or rate of heart contraction.
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Any process that modulates the rate, frequency or extent of release of sequestered calcium ion into cytosol by the sarcoplasmic reticulum, the process in which the release of sequestered calcium ion by sarcoplasmic reticulum into cytosol occurs via calcium release channels.
smooth muscle contraction A process in which force is generated within smooth muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. Smooth muscle differs from striated muscle in the much higher actin/myosin ratio, the absence of conspicuous sarcomeres and the ability to contract to a much smaller fraction of its resting length.

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
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
P27815 PDE4A cAMP-specific 3',5'-cyclic phosphodiesterase 4A Homo sapiens (Human) EV SS
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
Q08499 PDE4D cAMP-specific 3',5'-cyclic phosphodiesterase 4D Homo sapiens (Human) EV
O89084 Pde4a 3',5'-cyclic-AMP phosphodiesterase 4A Mus musculus (Mouse) SS
Q3UEI1 Pde4c cAMP-specific 3',5'-cyclic phosphodiesterase 4C Mus musculus (Mouse) PR
O70628 Pde9a High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Mus musculus (Mouse) PR
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
P23440 Pde6b Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Mus musculus (Mouse) PR
Q8CG03 Pde5a cGMP-specific 3',5'-cyclic phosphodiesterase Mus musculus (Mouse) SS
Q8QZV1 Pde9a High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Rattus norvegicus (Rat) PR
P14646 Pde4b cAMP-specific 3',5'-cyclic phosphodiesterase 4B Rattus norvegicus (Rat) SS
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
P54748 Pde4a 3',5'-cyclic-AMP phosphodiesterase 4A Rattus norvegicus (Rat) SS
Q9QYJ6 Pde10a cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Rattus norvegicus (Rat) PR
P14270 Pde4d cAMP-specific 3',5'-cyclic phosphodiesterase 4D Rattus norvegicus (Rat) PR
Q22000 pde-4 Probable 3',5'-cyclic phosphodiesterase pde-4 Caenorhabditis elegans PR
10 20 30 40 50 60
MERDTCDVLS RSKSASEETL HSCNEEEDPF RGMEPYLVRR LSSRSIQLPP LAFRQLEQAD
70 80 90 100 110 120
LRSESENIPR PTSLPLKILP LIAVTSADSS GFDVDNGTSA GRSPLDPMTS PGSGLILQAN
130 140 150 160 170 180
FVHSQRRESF LYRSDSDYDL SPKSMSRNSS IASDIHGDDL IVTPFAQVLA SLRTVRNNFA
190 200 210 220 230 240
ALTNLQDRAP SKRSPMCNQP SINKATITEE AYQKLASETL EELDWCLDQL ETLQTRHSVS
250 260 270 280 290 300
EMASNKFKRM LNRELTHLSE MSRSGNQVSE YISNTFLDKQ HEVEIPSPTQ KEKEKKKRPM
310 320 330 340 350 360
SQISGVKKLM HSSSLTNSCI PRFGVKTEQE DVLAKELEDV NKWGLHVFRI AELSGNRPLT
370 380 390 400 410 420
VIMHTIFQER DLLKTFKIPV DTLITYLMTL EDHYHADVAY HNNIHAADVV QSTHVLLSTP
430 440 450 460 470 480
ALEAVFTDLE ILAAIFASAI HDVDHPGVSN QFLINTNSEL ALMYNDSSVL ENHHLAVGFK
490 500 510 520 530 540
LLQEENCDIF QNLTKKQRQS LRKMVIDIVL ATDMSKHMNL LADLKTMVET KKVTSSGVLL
550 560 570 580 590 600
LDNYSDRIQV LQNMVHCADL SNPTKPLQLY RQWTDRIMEE FFRQGDRERE RGMEISPMCD
610 620 630 640 650 660
KHNASVEKSQ VGFIDYIVHP LWETWADLVH PDAQDILDTL EDNREWYQST IPQSPSPAPD
670 680 690 700 710 720
DQEEGRQGQT EKFQFELTLE EDCESDTEKD SGSQVEEDTS CSDSKTLCTQ DSESTEIPLD
730 740
EQVEEEAVAE EESQPETCVP DDCCPDT