O89084
SS
Gene name |
Pde4a |
Protein name |
3',5'-cyclic-AMP phosphodiesterase 4A |
Names |
EC 3.1.4.53 , cAMP-specific phosphodiesterase 4A |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:18577 |
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)
Target domain |
343-672 (3'5'-cyclic nucleotide phosphodiesterase, catalytic domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Burgin AB et al. (2010) "Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety", Nature biotechnology, 28, 63-70
- Beard MB et al. (2000) "UCR1 and UCR2 domains unique to the cAMP-specific phosphodiesterase family form a discrete module via electrostatic interactions", The Journal of biological chemistry, 275, 10349-58
- Houslay MD et al. (2010) "Putting the lid on phosphodiesterase 4", Nature biotechnology, 28, 38-40
Autoinhibited structure
Activated structure
1 structures for O89084
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O89084-F1 | Predicted | AlphaFoldDB |
42 variants for O89084
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3399972760 | 8 | S>A | No | EVA | |
| rs3389035107 | 109 | P>A | No | EVA | |
| rs1133413114 | 119 | D>G | No | EVA | |
| rs1134602780 | 121 | Q>H | No | EVA | |
| rs1134237134 | 121 | Q>P | No | EVA | |
| rs3399784492 | 124 | P>Q | No | EVA | |
| rs3389020931 | 136 | Q>P | No | EVA | |
| rs3389002706 | 144 | R>C | No | EVA | |
| rs3389029942 | 151 | M>I | No | EVA | |
| rs3389026357 | 165 | E>V | No | EVA | |
| rs3389019695 | 179 | V>M | No | EVA | |
| rs3389019662 | 192 | L>F | No | EVA | |
| rs3389015422 | 227 | R>Q | No | EVA | |
| rs3389008215 | 262 | N>I | No | EVA | |
| rs3389019625 | 277 | Q>H | No | EVA | |
| rs3399338892 | 323 | T>* | No | EVA | |
| rs3389026335 | 325 | L>M | No | EVA | |
| rs3389019623 | 358 | L>S | No | EVA | |
| rs3389019624 | 374 | G>V | No | EVA | |
| rs3389008203 | 383 | T>M | No | EVA | |
| rs3389008273 | 409 | E>D | No | EVA | |
| rs3388996490 | 436 | A>V | No | EVA | |
| rs3389015366 | 439 | A>T | No | EVA | |
| rs3389032866 | 455 | A>T | No | EVA | |
| rs3389008207 | 474 | T>S | No | EVA | |
| rs3389035134 | 553 | S>I | No | EVA | |
| rs3389028797 | 599 | F>Y | No | EVA | |
| rs3389026801 | 601 | Q>H | No | EVA | |
| rs3389028917 | 602 | Q>L | No | EVA | |
| rs3389032802 | 624 | V>M | No | EVA | |
| rs3388975809 | 635 | I>T | No | EVA | |
| rs3388996507 | 637 | H>N | No | EVA | |
| rs3389035146 | 637 | H>Q | No | EVA | |
| rs3389026813 | 657 | T>A | No | EVA | |
| rs37463219 | 685 | S>G | No | EVA | |
| rs259561254 | 707 | S>P | No | EVA | |
| rs37263260 | 717 | E>D | No | EVA | |
| rs3389002697 | 754 | T>I | No | EVA | |
| rs3399874059 | 802 | A>P | No | EVA | |
| rs3389029000 | 804 | V>M | No | EVA | |
| rs3389035163 | 823 | T>I | No | EVA | |
| rs3389020901 | 826 | D>E | No | EVA |
No associated diseases with O89084
4 regional properties for O89084
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain | 343 - 672 | IPR002073 |
| domain | HD/PDEase domain | 416 - 600 | IPR003607 |
| conserved_site | 3'5'-cyclic nucleotide phosphodiesterase, conserved site | 459 - 470 | IPR023174 |
| domain | Phosphodiesterase 4 upstream conserved regions (UCR) | 173 - 288 | IPR040844 |
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 | |
8 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. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| 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. |
| 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. |
7 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. |
| 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 |
| 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 |
| 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 |
| 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 |
| P54748 | Pde4a | 3',5'-cyclic-AMP phosphodiesterase 4A | Rattus norvegicus (Rat) | SS |
| Q22000 | pde-4 | Probable 3',5'-cyclic phosphodiesterase pde-4 | Caenorhabditis elegans | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MEPPAAPSER | SLSLSLPGPR | EGQATLKPPP | QHLWRQPRTP | IRIQQRGYSD | SAERSEPERS |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PHRPIERADA | VDTGDRPGLR | TTRMSWPSSF | HGTGTGGGSS | RRLEAENGPT | PSPGRSPLDS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| QASPGLMLHA | GAATSQRRES | FLYRSDSDYD | MSPKTMSRNS | SVASEAHGED | LIVTPFAQVL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| ASLRNVRSNF | SLLTNVPIPS | NKRSPLGGPP | SVCKATLSEE | TCQQLARETL | EELDWCLEQL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ETMQTYRSVS | EMASHKFKRM | LNRELTHLSE | MSRSGNQVSE | YISNTFLDKQ | HEVEIPSPTP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RQRPFQQPPP | AAVQQAQPMS | QITGLKKLVH | TGSLNINVPR | FGVKTDQEDL | LAQELENLSK |
| 370 | 380 | 390 | 400 | 410 | 420 |
| WGLNIFCVSE | YAGGRSLSCI | MYTIFQERDL | LKKFHIPVDT | MMTYMLTLED | 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 | QSPSPTLEEE | PGVLSDPALP | DKFQFELTLE | EEDEEDSLEV | PGLPCTEETL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| LAPHDTRAQA | MEQSKVKGQS | PAVVEVAESL | KQETASAHGA | PEESAEAVGH | SFSLETSILP |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DLRTLSPSEE | AQGLLGLPSM | AAEVEAPRDH | LAAMRACSAC | SGTSGDNSAV | ISAPGRWGSG |
| GDPA |