Q8CG03
SS
Gene name |
Pde5a (Pde5) |
Protein name |
cGMP-specific 3',5'-cyclic phosphodiesterase |
Names |
EC 3.1.4.35 , cGMP-binding cGMP-specific phosphodiesterase , CGB-PDE |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:242202 |
EC number |
3.1.4.35: Phosphoric diester hydrolases |
Protein Class |
|
Descriptions
PDE5A plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. PDE5A contains a catalytic domain that hydrolyzes cGMP and a regulatory (R) domain (1-539) that contains two GAFs, a and b. The R domain binds cGMP allosterically, provides for dimerization, and is phosphorylated at a site regulated by allosteric cGMP binding. The sequence containing GAF b and its flanking amino acids (403-539) autoinhibits the cGMP-binding affinity of GAF a.
Autoinhibitory domains (AIDs)
Target domain |
228-311 (GAF a domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Zoraghi R et al. (2005) "Structural and functional features in human PDE5A1 regulatory domain that provide for allosteric cGMP binding, dimerization, and regulation", The Journal of biological chemistry, 280, 12051-63
- Francis SH et al. (2011) "Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions", Physiological reviews, 91, 651-90
Autoinhibited structure
Activated structure
2 structures for Q8CG03
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2K31 | NMR | - | A | 154-320 | PDB |
| AF-Q8CG03-F1 | Predicted | AlphaFoldDB |
48 variants for Q8CG03
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388661788 | 15 | R>W | No | EVA | |
| rs3388664702 | 19 | W>C | No | EVA | |
| rs3388654274 | 21 | E>V | No | EVA | |
| rs3388662390 | 47 | W>C | No | EVA | |
| rs3413041530 | 57 | V>G | No | EVA | |
| rs3388660746 | 70 | S>F | No | EVA | |
| rs3388650255 | 74 | Q>* | No | EVA | |
| rs3388660734 | 86 | A>S | No | EVA | |
| rs3388665523 | 96 | F>I | No | EVA | |
| rs3388649679 | 98 | R>P | No | EVA | |
| rs3388658158 | 117 | D>N | No | EVA | |
| rs3388658912 | 146 | V>I | No | EVA | |
| rs3388654339 | 147 | K>* | No | EVA | |
| rs3388660762 | 147 | K>I | No | EVA | |
| rs3388660745 | 199 | E>K | No | EVA | |
| rs3388650230 | 244 | E>G | No | EVA | |
| rs3388650208 | 316 | E>G | No | EVA | |
| rs3388655794 | 377 | E>A | No | EVA | |
| rs3388660796 | 384 | P>L | No | EVA | |
| rs3388660802 | 428 | E>D | No | EVA | |
| rs3388663623 | 440 | S>I | No | EVA | |
| rs3388649670 | 450 | K>N | No | EVA | |
| rs3388661863 | 451 | K>M | No | EVA | |
| rs3388655720 | 474 | F>I | No | EVA | |
| rs3388661856 | 479 | E>* | No | EVA | |
| rs3388661814 | 484 | A>P | No | EVA | |
| rs3388654273 | 543 | T>S | No | EVA | |
| rs3388658184 | 545 | K>N | No | EVA | |
| rs3388664712 | 545 | K>Q | No | EVA | |
| rs3388654271 | 546 | I>T | No | EVA | |
| rs3388659013 | 548 | D>H | No | EVA | |
| rs3388665522 | 615 | M>I | No | EVA | |
| rs3388662796 | 623 | K>M | No | EVA | |
| rs3388664704 | 670 | I>T | No | EVA | |
| rs3388661828 | 671 | M>T | No | EVA | |
| rs3388663622 | 721 | R>K | No | EVA | |
| rs3388662773 | 726 | F>L | No | EVA | |
| rs3393592753 | 738 | D>E | No | EVA | |
| rs3393636104 | 739 | P>A | No | EVA | |
| rs3393527848 | 739 | P>H | No | EVA | |
| rs3388662813 | 769 | A>T | No | EVA | |
| rs3388658161 | 776 | F>I | No | EVA | |
| rs3388658161 | 776 | F>V | No | EVA | |
| rs3393621120 | 778 | D>E | No | EVA | |
| rs3393636114 | 819 | Y>R | No | EVA | |
| rs3388658584 | 832 | L>G | No | EVA | |
| rs3388662762 | 836 | C>R | No | EVA | |
| rs47067178 | 853 | M>L | No | EVA |
No associated diseases with Q8CG03
5 regional properties for Q8CG03
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain | 526 - 850 | IPR002073 |
| domain | GAF domain | 154 - 314 | IPR003018-1 |
| domain | GAF domain | 336 - 503 | IPR003018-2 |
| domain | HD/PDEase domain | 600 - 777 | IPR003607 |
| conserved_site | 3'5'-cyclic nucleotide phosphodiesterase, conserved site | 643 - 654 | IPR023174 |
Functions
| Description | ||
|---|---|---|
| EC Number | 3.1.4.35 | Phosphoric diester hydrolases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
No GO annotations of cellular component
| Name | Definition |
|---|---|
| No GO annotations for cellular component |
6 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 |
| cGMP binding | Binding to cGMP, the nucleotide cyclic GMP (guanosine 3',5'-cyclophosphate). |
| cyclic-nucleotide phosphodiesterase activity | Catalysis of the reaction |
| metal ion binding | Binding to a metal ion. |
18 GO annotations of biological process
| Name | Definition |
|---|---|
| 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. |
| cGMP catabolic process | The chemical reactions and pathways resulting in the breakdown of cyclic GMP, guanosine 3',5'-phosphate. |
| cGMP metabolic process | The chemical reactions and pathways involving cyclic GMP, guanosine 3',5'-phosphate. |
| negative regulation of cardiac muscle contraction | Any process that stops, prevents, or reduces the frequency, rate or extent of cardiac muscle contraction. |
| negative regulation of T cell proliferation | Any process that stops, prevents or reduces the rate or extent of T cell proliferation. |
| oocyte development | The process whose specific outcome is the progression of an oocyte over time, from initial commitment of the cell to its specific fate, to the fully functional differentiated cell. |
| positive regulation of apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. |
| positive regulation of cardiac muscle hypertrophy | Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division. |
| positive regulation of chronic inflammatory response | Any process that activates or increases the frequency, rate, or extent of a chronic inflammatory response. |
| positive regulation of G protein-coupled receptor signaling pathway | Any process that activates or increases the frequency, rate or extent of G protein-coupled receptor signaling pathway activity. |
| positive regulation of MAP kinase activity | Any process that activates or increases the frequency, rate or extent of MAP kinase activity. |
| positive regulation of oocyte development | Any process that increases the rate or extent of the process whose specific outcome is the progression of an oocyte over time, from initial commitment of the cell to its specific fate, to the fully functional differentiated cell. |
| positive regulation of vasoconstriction | Any process that activates or increases the frequency, rate or extent of vasoconstriction. |
| regulation of nitric oxide mediated signal transduction | Any process that modulates the rate, frequency or extent of nitric oxide mediated signal transduction. Nitric oxide mediated signal transduction is The series of molecular signals mediated by the detection of nitric oxide (NO). |
| regulation of the force of heart contraction | Any process that modulates the extent of heart contraction, changing the force with which blood is propelled. |
| relaxation of cardiac muscle | The process in which the extent of cardiac muscle contraction is reduced. |
| short-term memory | The memory process that deals with the storage, retrieval and modification of information received a short time (up to about 30 minutes) ago. This type of memory is typically dependent on direct, transient effects of second messenger activation. |
| T cell proliferation | The expansion of a T cell population by cell division. Follows T cell activation. |
33 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P23439 | PDE6B | Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta | Bos taurus (Bovine) | PR |
| Q28156 | PDE5A | cGMP-specific 3',5'-cyclic phosphodiesterase | Bos taurus (Bovine) | SS |
| 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 |
| O77746 | PDE5A | cGMP-specific 3',5'-cyclic phosphodiesterase | Canis lupus familiaris (Dog) (Canis familiaris) | SS |
| Q9W4T4 | dnc | 3',5'-cyclic-AMP phosphodiesterase, isoform I | Drosophila melanogaster (Fruit fly) | SS |
| Q9VJ79 | Pde11 | Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11 | 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 |
| 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 |
| O76074 | PDE5A | cGMP-specific 3',5'-cyclic phosphodiesterase | Homo sapiens (Human) | EV |
| P0C1Q2 | Pde11a | Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A | Mus musculus (Mouse) | SS |
| 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 |
| 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 |
| P23440 | Pde6b | Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta | Mus musculus (Mouse) | PR |
| 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 |
| 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 |
| O54735 | Pde5a | cGMP-specific 3',5'-cyclic phosphodiesterase | Rattus norvegicus (Rat) | SS |
| Q22000 | pde-4 | Probable 3',5'-cyclic phosphodiesterase pde-4 | Caenorhabditis elegans | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MERAGPNSVR | SQQQRDPDWV | EAWLDDHRDF | TFSYFIRKAT | RDMVNAWFSE | RVHNIPVCKE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GIRAHTESCS | CSLQQSPHAD | NTTPGAPARK | ISASEFDRPL | RPIVVKDSEG | TVSFLSDSGK |
| 130 | 140 | 150 | 160 | 170 | 180 |
| KEQMPLTPPR | FDSDEGDQCS | RLLELVKDIS | SHLDVTALCH | KIFLHIHGLI | SADRYSLFLV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| CEDSSKDKFL | ISRLFDVAEG | STLEEASNNC | IRLEWNKGIV | GHVAAFGEPL | NIKDAYEDPR |
| 250 | 260 | 270 | 280 | 290 | 300 |
| FNAEVDQITG | YKTQSILCMP | IKNHREEVVG | VAQAINKKSG | NGGTFTEKDE | KDFAAYLAFC |
| 310 | 320 | 330 | 340 | 350 | 360 |
| GIVLHNAQLY | ETSLLENKRN | QVLLDLASLI | FEEQQSLEVI | LKKIAATIIS | FMQVQKCTIF |
| 370 | 380 | 390 | 400 | 410 | 420 |
| IVDEDCPDSF | SRVFHMECEE | VGKPSDPLTR | EQDANKINYM | YAQYVKNTME | PLNIPDVTKD |
| 430 | 440 | 450 | 460 | 470 | 480 |
| KRFPWTNENM | GHVNTPCIGS | LLCTPIKNGK | KNKVIGVCQL | VNKMEENTGK | IKAFNQNDEQ |
| 490 | 500 | 510 | 520 | 530 | 540 |
| FLEAFVIFCG | LGIQNTQMYE | AVERAMAKQM | VTLEVLSYHA | SAAEEETREL | QALSAAVVPS |
| 550 | 560 | 570 | 580 | 590 | 600 |
| AQTLKITDFS | FSDFELSDLE | TALCTIRMFT | DLNLVQNFQM | KHEVLCRWIL | SVKKNYRKNV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| AYHNWRHAFN | TAQCMFAALK | AGKIQNKLTD | LETLALLIAA | LSHDLDHRGV | NNSYIQRSEH |
| 670 | 680 | 690 | 700 | 710 | 720 |
| PLAQLYCHSI | MEHHHFDQCL | MILNSPGNQI | LSGLSIDEYK | TTLKIIKQAI | LATDLALYIK |
| 730 | 740 | 750 | 760 | 770 | 780 |
| RRGEFFELIR | KNQFSFEDPL | QKELFLAMLM | TACDLSAITK | PWPIQQRIAE | LVAAEFFDQG |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DRERKELNME | PADLMNREKK | NKIPSMQVGF | IDAICLQLYE | ALTHVSEDCL | PLLDGCRKNR |
| 850 | 860 | ||||
| QKWQALAEQQ | EKMLLNGESS | QGKRD |