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The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]
PDE4A (Phosphodiesterase 4A) is a Protein Coding gene. Diseases associated with PDE4A include Asthma and Pulmonary Eosinophilia. Among its related pathways are ADP signalling through P2Y purinoceptor 12 and Sweet Taste Signaling. Gene Ontology (GO) annotations related to this gene include 3',5'-cyclic-nucleotide phosphodiesterase activity and 3',5'-cyclic-AMP phosphodiesterase activity. An important paralog of this gene is PDE4D.
Phosphodiesterases (PDEs) are a family of phosphohydrolyases that catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). PDEs regulate the second messengers by controlling their degradation.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004114 | 3',5'-cyclic-nucleotide phosphodiesterase activity | IEA | -- |
GO:0004115 | 3',5'-cyclic-AMP phosphodiesterase activity | TAS,IGI | 8413254 |
GO:0005515 | protein binding | IPI | 11306681 |
GO:0008081 | phosphoric diester hydrolase activity | IEA | -- |
GO:0016787 | hydrolase activity | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005654 | nucleoplasm | IDA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005829 | cytosol | TAS | -- |
GO:0005886 | plasma membrane | IEA,IDA | -- |
GO:0016020 | membrane | TAS | 9677330 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Signaling by GPCR | ||
2 | Sweet Taste Signaling |
Cellular Effects of Sildenafil
.46
|
Sperm Motility
.37
|
3 | DAG and IP3 signaling | ||
4 | cAMP signaling pathway | ||
5 | Metabolism |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006198 | cAMP catabolic process | IEA | -- |
GO:0007165 | signal transduction | TAS | 8940140 |
GO:0007186 | G protein-coupled receptor signaling pathway | TAS | -- |
GO:0007608 | sensory perception of smell | IEA | -- |
GO:0010738 | regulation of protein kinase A signaling | IEA | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Dipyridamole | Approved | Pharma | Inhibitor, Inhibition, Target, inhibitor | Adenosine transport inhibitor | 93 | |
Dyphylline | Approved | Pharma | Target, inhibitor | 0 | ||
Roflumilast | Approved | Pharma | Target, inhibitor | PDE-4 inhibitor | 0 | |
Theophylline | Approved | Pharma | Antagonist, Target, inhibitor, antagonist | 75 | ||
Enprofylline | Approved, Experimental | Pharma | Target, inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
IBMX |
|
Antagonist | 28822-58-4 |
|
||
Ro201724 |
|
Inhibitor, Inhibition |
|
|||
Eggmanone |
|
505068-32-6 |
|
|
||
Etazolate hydrochloride |
|
35838-58-5 |
|
|
||
MY-5445 |
|
78351-75-4 |
|
|
Compound | Action | Cas Number |
---|---|---|
Eggmanone | Potent and selective PDE4 inhibitor; suppresses hedgehog signaling | 505068-32-6 |
Etazolate hydrochloride | PDE4 inhibitor | 35838-58-5 |
IBMX | PDE inhibitor (non-selective) | 28822-58-4 |
MY-5445 | PDE5 inhibitor | 78351-75-4 |
Ro 20-1724 | PDE4 inhibitor | 29925-17-5 |
Compound | Action | Cas Number |
---|---|---|
Aminophylline | 317-34-0 | |
AN-2728 | PDE4 inhibitor,anti-inflammatory compound | 906673-24-3 |
Anagrelide HCl | Thrombocytopenic agent | 58579-51-4 |
Apremilast (CC-10004) | PDE4 inhibitor | 608141-41-9 |
CDP 840 hydrochloride | PDE4 inhibitor,potent and selective | 162542-90-7 |
Cilomilast | Potent PDE4 inhibitor | 153259-65-5 |
Deltarasin | KRAS-PDEδ interaction inhibitor | 1440898-61-2 |
Dipyridamole | 58-32-2 | |
Doxofylline | 69975-86-6 | |
Dyphylline | 479-18-5 | |
GSK256066 | PDE4-inhibitor,selective and highly potent | 801312-28-7 |
Irsogladine | PDE4 inhibitor | 57381-26-7 |
Pimobendan hydrochloride | 77469-98-8 | |
Roflumilast | PDE-4 inhibitor | 162401-32-3 |
Rolipram | PDE4-inhibitor and an anti-inflammatory agent | 61413-54-5 |
S- (+)-Rolipram | CAMP-specific PDE4 inhibitor | 85416-73-5 |
Vinpocetine | PDE inhibitor | 42971-09-5 |
Zardaverine | PDE III and IV inhibitor | 101975-10-4 |
ExUns: | 1 | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10a | · | 10b | ^ | 11a | · | 11b | ^ | 12 | ^ | 13a | · | 13b | ^ | 14a | · | 14b | ^ | 15 | ^ | 16 | ^ | 17a | · | 17b | · | 17c | ^ | 18a | · | 18b | ^ | 19a | · |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP3: | - | - | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP5: | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | - | - | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP9: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP10: | - |
ExUns: | 19b | · | 19c | · | 19d |
---|---|---|---|---|---|
SP1: | |||||
SP2: | |||||
SP3: | |||||
SP4: | |||||
SP5: | |||||
SP6: | |||||
SP7: | |||||
SP8: | |||||
SP9: | |||||
SP10: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Dog (Canis familiaris) |
Mammalia | PDE4A 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | PDE4A 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Pde4a 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Pde4a 30 17 31 |
|
OneToOne | |
Chimpanzee (Pan troglodytes) |
Mammalia | PDE4A 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | PDE4A 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | PDE4A 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100488846 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | pde4a 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | dnc 32 |
|
|
|
Worm (Caenorhabditis elegans) |
Secernentea | R153.1a 32 |
|
|
SNP ID | Clinical significance and condition | Chr 19 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
710380 | Benign: not provided | 10,420,815(+) | C/T | SYNONYMOUS_VARIANT,INTRON_VARIANT | |
713585 | Likely Benign: not provided | 10,459,411(+) | C/T | SYNONYMOUS_VARIANT | |
723426 | Likely Benign: not provided | 10,467,240(+) | G/C | SYNONYMOUS_VARIANT | |
735287 | Likely Benign: not provided | 10,459,474(+) | C/T | SYNONYMOUS_VARIANT | |
735288 | Likely Benign: not provided | 10,467,011(+) | G/A | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
asthma |
|
|
pulmonary eosinophilia |
|
|
pulmonary disease, chronic obstructive |
|
|
platelet adenylate cyclase activity |
|
|
respiratory failure |
|