Q28156
SS
Gene name |
PDE5A (PDE5) |
Protein name |
cGMP-specific 3',5'-cyclic phosphodiesterase |
Names |
cGMP-binding cGMP-specific phosphodiesterase, CGB-PDE |
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:281972 |
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 GAF a cGMP-binding affinity.
Autoinhibitory domains (AIDs)
Target domain |
154-314 (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
- Houslay MD et al. (2010) "Putting the lid on phosphodiesterase 4", Nature biotechnology, 28, 38-40
- 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
- Burgin AB et al. (2010) "Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety", Nature biotechnology, 28, 63-70
Autoinhibited structure
Activated structure
3 structures for Q28156
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 3JAB | EM | 1100 A | C/O | 525-850 | PDB |
| 3JBQ | EM | 1100 A | B/F | 525-850 | PDB |
| AF-Q28156-F1 | Predicted | AlphaFoldDB |
89 variants for Q28156
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs472912578 | 4 | A>G | No | Ensembl | |
| rs455996511 | 4 | A>P | No | Ensembl | |
| rs458219443 | 11 | P>T | No | Ensembl | |
| rs471823299 | 12 | Q>H | No | Ensembl | |
| rs439237901 | 13 | Q>E | No | Ensembl | |
| rs482412424 | 23 | W>R | No | Ensembl | |
| rs448029362 | 28 | W>G | No | Ensembl | |
| rs462052351 | 29 | D>N | No | Ensembl | |
| rs464288761 | 33 | S>P | No | Ensembl | |
| rs450189570 | 39 | G>A | No | Ensembl | |
| rs478018804 | 39 | G>C | No | Ensembl | |
| rs470311730 | 40 | T>P | No | Ensembl | |
| rs468976301 | 46 | A>V | No | Ensembl | |
| rs482890939 | 49 | A>V | No | Ensembl | |
| rs721894563 | 58 | C>Y | No | Ensembl | |
| rs437811583 | 87 | P>Q | No | Ensembl | |
| rs455000935 | 88 | T>A | No | Ensembl | |
| rs434076935 | 89 | R>S | No | Ensembl | |
| rs454085349 | 91 | I>N | No | Ensembl | |
| rs439904908 | 93 | A>D | No | Ensembl | |
| rs471002961 | 93 | A>S | No | Ensembl | |
| rs469341795 | 129 | P>Q | No | Ensembl | |
| rs442233611 | 158 | L>I | No | Ensembl | |
| rs476826562 | 201 | S>A | No | Ensembl | |
| rs445882534 | 204 | E>G | No | Ensembl | |
| rs469141643 | 214 | E>A | No | Ensembl | |
| rs437790534 | 215 | W>S | No | Ensembl | |
| rs448142098 | 224 | A>G | No | Ensembl | |
| rs434040812 | 228 | E>D | No | Ensembl | |
| rs454242697 | 231 | N>T | No | Ensembl | |
| rs433190048 | 236 | Y>F | No | Ensembl | |
| rs470961623 | 236 | Y>N | No | Ensembl | |
| rs522282321 | 237 | E>G | No | Ensembl | |
| rs456820390 | 237 | E>Q | No | Ensembl | |
| rs480537454 | 245 | V>G | No | Ensembl | |
| rs470119173 | 245 | V>I | No | Ensembl | |
| rs434746732 | 246 | D>A | No | Ensembl | |
| rs466207737 | 246 | D>Y | No | Ensembl | |
| rs451694035 | 248 | I>T | No | Ensembl | |
| rs454278555 | 285 | F>L | No | Ensembl | |
| rs470779692 | 295 | A>T | No | Ensembl | |
| rs439380871 | 319 | R>S | No | Ensembl | |
| rs462758398 | 321 | Q>L | No | Ensembl | |
| rs447418170 | 322 | V>G | No | Ensembl | |
| rs477843310 | 327 | A>P | No | Ensembl | |
| rs470033126 | 328 | S>N | No | Ensembl | |
| rs455418452 | 330 | I>M | No | Ensembl | |
| rs452805272 | 345 | A>P | No | Ensembl | |
| rs434865459 | 357 | C>G | No | Ensembl | |
| rs451734868 | 362 | V>M | No | Ensembl | |
| rs465828686 | 427 | N>I | No | Ensembl | |
| rs465828686 | 427 | N>T | No | Ensembl | |
| rs434833712 | 429 | N>D | No | Ensembl | |
| rs445345479 | 435 | Q>E | No | Ensembl | |
| rs445345479 | 435 | Q>K | No | Ensembl | |
| rs1116709219 | 467 | T>S | No | Ensembl | |
| rs437896673 | 491 | L>F | No | Ensembl | |
| rs464400810 | 493 | I>V | No | Ensembl | |
| rs433267723 | 495 | N>K | No | Ensembl | |
| rs456569574 | 502 | V>G | No | Ensembl | |
| rs476739362 | 510 | M>K | No | Ensembl | |
| rs441931219 | 511 | V>I | No | Ensembl | |
| rs435077547 | 547 | T>A | No | Ensembl | |
| rs451956356 | 572 | L>R | No | Ensembl | |
| rs797584796 | 598 | K>E | No | Ensembl | |
| rs469676333 | 600 | V>I | No | Ensembl | |
| rs465905453 | 658 | S>R | No | Ensembl | |
| rs479581526 | 659 | E>* | No | Ensembl | |
| rs445375258 | 659 | E>D | No | Ensembl | |
| rs465426576 | 660 | H>L | No | Ensembl | |
| rs384987601 | 663 | A>S | No | Ensembl | |
| rs437200200 | 666 | Y>S | No | Ensembl | |
| rs457260474 | 676 | F>Y | No | Ensembl | |
| rs453555551 | 679 | C>F | No | Ensembl | |
| rs436657021 | 679 | C>S | No | Ensembl | |
| rs473418780 | 680 | L>V | No | Ensembl | |
| rs483311532 | 687 | G>S | No | Ensembl | |
| rs468820288 | 699 | Y>D | No | Ensembl | |
| rs479170498 | 702 | T>S | No | Ensembl | |
| rs446566375 | 704 | K>M | No | Ensembl | |
| rs466621022 | 711 | L>F | No | Ensembl | |
| rs464254973 | 721 | R>I | No | Ensembl | |
| rs478089482 | 721 | R>S | No | Ensembl | |
| rs449801317 | 722 | R>* | No | Ensembl | |
| rs470327035 | 732 | N>I | No | Ensembl | |
| rs1117151163 | 789 | I>R | No | Ensembl | |
| rs1118040137 | 817 | Q>E | No | Ensembl | |
| rs378574450 | 817 | Q>E | No | Ensembl | |
| rs448011043 | 860 | S>G | No | Ensembl |
No associated diseases with Q28156
5 regional properties for Q28156
| 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 |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| 3',5'-cyclic-GMP phosphodiesterase activity | Catalysis of the reaction: 3',5'-cyclic GMP + H2O = GMP + H+. |
| 3',5'-cyclic-nucleotide phosphodiesterase activity | Catalysis of the reaction: a nucleoside 3',5'-cyclic phosphate + H2O = a nucleoside 5'-phosphate. |
| cGMP binding | Binding to cGMP, the nucleotide cyclic GMP (guanosine 3',5'-cyclophosphate). |
| cyclic-nucleotide phosphodiesterase activity | Catalysis of the reaction: a nucleoside cyclic phosphate + H2O = a nucleoside phosphate. |
| metal ion binding | Binding to a metal ion. |
2 GO annotations of biological process
| Name | Definition |
|---|---|
| cGMP catabolic process | The chemical reactions and pathways resulting in the breakdown of cyclic GMP, guanosine 3',5'-phosphate. |
| 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. |
34 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P14100 | PDE1A | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A | Bos taurus (Bovine) | PR |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| MERAGPGSAR | PQQQWDQDSV | EAWLDDHWDF | TFSYFVRKGT | REMVNAWFAE | RVHTIPVCKE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GIKGHTESCS | CPLQPSPRAE | SSVPGTPTRK | ISASEFDRPL | RPIVIKDSEG | TVSFLSDSDK |
| 130 | 140 | 150 | 160 | 170 | 180 |
| KEQMPLTSPR | FDNDEGDQCS | RLLELVKDIS | SHLDVTALCH | KIFLHIHGLI | SADRYSLFLV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| CEDSSNDKFL | 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 |
| IVDEDCSDSF | SSVFHMECEE | LEKSSDTLTR | ERDANRINYM | YAQYVKNTME | PLNIPDVSKD |
| 430 | 440 | 450 | 460 | 470 | 480 |
| KRFPWTNENM | GNINQQCIRS | LLCTPIKNGK | KNKVIGVCQL | VNKMEETTGK | VKAFNRNDEQ |
| 490 | 500 | 510 | 520 | 530 | 540 |
| FLEAFVIFCG | LGIQNTQMYE | AVERAMAKQM | VTLEVLSYHA | SAAEEETREL | QSLAAAVVPS |
| 550 | 560 | 570 | 580 | 590 | 600 |
| AQTLKITDFS | FSDFELSDLE | TALCTIRMFT | DLNLVQNFQM | KHEVLCKWIL | SVKKNYRKNV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| AYHNWRHAFN | TAQCMFAALK | AGKIQKRLTD | LEILALLIAA | LSHDLDHRGV | NNSYIQRSEH |
| 670 | 680 | 690 | 700 | 710 | 720 |
| PLAQLYCHSI | MEHHHFDQCL | MILNSPGNQI | LSGLSIEEYK | TTLKIIKQAI | LATDLALYIK |
| 730 | 740 | 750 | 760 | 770 | 780 |
| RRGEFFELIM | KNQFNLEDPH | QKELFLAMLM | TACDLSAITK | PWPIQQRIAE | LVATEFFDQG |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DRERKELNIE | PADLMNREKK | NKIPSMQVGF | IDAICLQLYE | ALTHVSEDCF | PLLDGCRKNR |
| 850 | 860 | ||||
| QKWQALAEQQ | EKTLINGESS | QTKRN |