PDE3A

This gene encodes 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]
Diseases associated with PDE3A include Hypertension And Brachydactyly Syndrome and Stroke, Ischemic. Among its related pathways are Activation of cAMP-Dependent PKA 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 PDE3B.
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, 25961942, 8155697, 8695850).
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, 34707099).
Inhibited by cGMP (PubMed:8155697, 8695850).
Inhibited by 17beta-estradiol (PubMed:35104454).
Inhibited by milrinone (PubMed:27975297).
cAMP,cGMP inhibited nucleotide phosphodiesterase 3A homolog,involved in fat metabolism
Cell Membrane; Multi-pass membrane protein {ECO:0000250 UniProtKB:Q9Z0X4 | ECO:0000255}4
Cytoplasm, cytosol {ECO:0000269 PubMed:35104454}5
Quaternary structure:
Homodimer (PubMed:34272366, 8155697).
Interacts with SLFN12; direct low affinity interaction which is stimulated by binding of 17beta-estradiol/E2 to PDE3A and that positively regulates the ribonuclease activity of SLFN12 (PubMed:31420216, 34272366, 34707099, 35104454).