PDE3A

PDE3A is a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes hydrolyze both cAMP and cGMP, and play critical roles in many cellular processes by regulating the amplitude and duration of intracellular cyclic nucleotide signals. The encoded protein mediates platelet aggregation and also plays important roles in cardiovascular function by regulating vascular smooth muscle contraction and relaxation. Inhibitors of the encoded protein may be effective in treating congestive heart failure.

Full Name

phosphodiesterase 3A, cGMP-inhibited

Function

Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:8695850, PubMed:8155697, PubMed:25961942).
Has also activity toward cUMP (PubMed:27975297).
Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099).

Biological Process

cAMP-mediated signalingManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to cGMPManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to transforming growth factor beta stimulusManual Assertion Based On ExperimentIEP:UniProtKB
cGMP-mediated signalingManual Assertion Based On ExperimentIMP:UniProtKB
G protein-coupled receptor signaling pathwayTAS:Reactome
Lipid metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of apoptotic processIEA:Ensembl
Negative regulation of cAMP-mediated signalingManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of vascular permeabilityManual Assertion Based On ExperimentIMP:UniProtKB
Oocyte maturationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of oocyte developmentManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of vascular permeabilityManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of meiotic nuclear divisionIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Membrane
Cytoplasm, cytosol

Involvement in disease

Hypertension and brachydactyly syndrome (HTNB):
A syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals.