P14270
PR
Gene name |
Pde4d |
Protein name |
cAMP-specific 3',5'-cyclic phosphodiesterase 4D |
Names |
DPDE3 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:24627 |
EC number |
3.1.4.53: Phosphoric diester hydrolases |
Protein Class |
|
Descriptions
(Annotation based on sequence homology with Q08499)
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 |
|
Relief mechanism |
|
Assay |
cis-regPred |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for P14270
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P14270-F1 | Predicted | AlphaFoldDB |
No variants for P14270
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P14270 | |||||
No associated diseases with P14270
3 regional properties for P14270
Functions
| Description | ||
|---|---|---|
| EC Number | 3.1.4.53 | Phosphoric diester hydrolases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
12 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| Golgi apparatus | A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it. |
| 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. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| 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 AMP + H2O = AMP + H+. |
| 3',5'-cyclic-nucleotide phosphodiesterase activity | Catalysis of the reaction: a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate. |
| 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. |
| cAMP binding | Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate). |
| cyclic-nucleotide phosphodiesterase activity | Catalysis of the reaction: a nucleoside cyclic phosphate + H2O = a nucleoside phosphate. |
| enzyme binding | Binding to an enzyme, a protein with catalytic activity. |
| heterocyclic compound binding | Binding to heterocyclic compound. |
| metal ion binding | Binding to a metal ion. |
| scaffold protein binding | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. |
| 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. |
35 GO annotations of biological process
| Name | Definition |
|---|---|
| adenylate cyclase-activating adrenergic receptor signaling pathway involved in positive regulation of heart rate | An adrenergic receptor signaling pathway that contributes to an increase in frequency or rate of heart contraction. Binding of adrenalin or noradrenalin to a beta-adrenergic receptor on the surface of the signal-receiving cell results in the activation of an intracellular Gs protein. Gs activates adenylate cyclase to increase intracellular cyclic-AMP (cAMP) levels. cAMP binds directly to F-channels to allow an inward flow of sodium (known as funny current, or If current). The funny current is responsible for membrane depolarization and an increase in heart rate. |
| 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. |
| aging | A developmental process that is a deterioration and loss of function over time. Aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Aging includes cellular senescence, but is more inclusive. May precede death and may succeed developmental maturation (GO:0021700). |
| cAMP catabolic process | The chemical reactions and pathways resulting in the breakdown of the nucleotide cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate). |
| 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 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. |
| leukocyte migration | The movement of a leukocyte within or between different tissues and organs of the body. |
| lung development | The process whose specific outcome is the progression of the lung over time, from its formation to the mature structure. In all air-breathing vertebrates the lungs are developed from the ventral wall of the oesophagus as a pouch which divides into two sacs. In amphibians and many reptiles the lungs retain very nearly this primitive sac-like character, but in the higher forms the connection with the esophagus becomes elongated into the windpipe and the inner walls of the sacs become more and more divided, until, in the mammals, the air spaces become minutely divided into tubes ending in small air cells, in the walls of which the blood circulates in a fine network of capillaries. In mammals the lungs are more or less divided into lobes, and each lung occupies a separate cavity in the thorax. |
| 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. |
| 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 interferon-gamma production | Any process that activates or increases the frequency, rate, or extent of interferon-gamma production. Interferon-gamma is also known as type II interferon. |
| positive regulation of interleukin-2 production | Any process that activates or increases the frequency, rate, or extent of interleukin-2 production. |
| positive regulation of interleukin-5 production | Any process that activates or increases the frequency, rate, or extent of interleukin-5 production. |
| 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 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 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. |
| regulation of ryanodine-sensitive calcium-release channel activity | Any process that modulates the activity of a ryanodine-sensitive calcium-release channel. The ryanodine-sensitive calcium-release channel catalyzes the transmembrane transfer of a calcium ion by a channel that opens when a ryanodine class ligand has been bound by the channel complex or one of its constituent parts. |
| regulation of signaling receptor activity | Any process that modulates the frequency, rate or extent of a signaling receptor activity. Receptor activity is when a molecule combines with an extracellular or intracellular messenger to initiate a change in cell activity. |
| signal transduction | The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell. |
| 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. |
| T cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell. |
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 |
| P23440 | Pde6b | Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta | Mus musculus (Mouse) | PR |
| O89084 | Pde4a | 3',5'-cyclic-AMP phosphodiesterase 4A | Mus musculus (Mouse) | SS |
| 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 |
| P54748 | Pde4a | 3',5'-cyclic-AMP phosphodiesterase 4A | Rattus norvegicus (Rat) | SS |
| P14646 | Pde4b | cAMP-specific 3',5'-cyclic phosphodiesterase 4B | Rattus norvegicus (Rat) | SS |
| 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 |
| MEAEGSSVPA | RAGSHEGSDS | SGGAALKAPK | HLWRHEQHHQ | YPLRQPQFRL | LHPHHHLPPP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PPPSPQPQLQ | PPPPPPLPPP | PPPPGATRGR | YASSGASRVR | HRGYSDTERY | LYCRAMDRTS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| YAVETGHRPG | LKKSRMSWPS | SFQGLRRFDV | DNGTSAGRSP | LDPMTSPGSG | LILQANFVHS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QRRESFLYRS | DSDYDLSPKS | MSRNSSIASD | IHGDDLIVTP | FAQVLASLRT | VRNNFAALTN |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LQDRAPSKRS | PMCNQPSINK | ATITEEAYQK | LASETLEELD | WCLDQLETLQ | TRHSVSEMAS |
| 310 | 320 | 330 | 340 | 350 | 360 |
| NKFKRMLNRE | LTHLSEMSRS | GNQVSEYISN | TFLDKQHEVE | IPSPTQKEKE | KKKRPMSQIS |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GVKKLMHSSS | LTNSCIPRFG | VKTEQEDVLA | KELEDVNKWG | LHVFRIAELS | GNRPLTVIMH |
| 430 | 440 | 450 | 460 | 470 | 480 |
| TIFQERDLLK | TFKIPVDTLI | TYLMTLEDHY | HADVAYHNNI | HAADVVQSTH | VLLSTPALEA |
| 490 | 500 | 510 | 520 | 530 | 540 |
| VFTDLEILAA | IFASAIHDVD | HPGVSNQFLI | NTNSELALMY | NDSSVLENHH | LAVGFKLLQE |
| 550 | 560 | 570 | 580 | 590 | 600 |
| ENCDIFQNLT | KKQRQSLRKM | AIDIVLATDM | SKHMNLLADL | KTMVETKKVT | SSGVLLLDNY |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SDRIQVLQNM | VHCADLSNPT | KPLQLYRQWT | DRIMEEFFRQ | GDRERERGME | ISPMCDKHNA |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SVEKSQVGFI | DYIVHPLWET | WADLVHPDAQ | DILDTLEDNR | EWYQSTIPQS | PSPAPDDQED |
| 730 | 740 | 750 | 760 | 770 | 780 |
| GRQGQTEKFQ | FELTLEEDGE | SDTEKDSGSQ | VEEDTSCSDS | KTLCTQDSES | TEIPLDEQVE |
| 790 | 800 | ||||
| EEAVAEEESQ | PQTGVADDCC | PDT |