PDE4D

PDE4D is one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.

Full Name

Phosphodiesterase 4D

Function

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Biological Process

Adenylate cyclase-activating adrenergic receptor signaling pathway involved in positive regulation of heart rateIC:BHF-UCL
Adrenergic receptor signaling pathwayISS:BHF-UCL
cAMP catabolic processManual Assertion Based On ExperimentIBA:GO_Central
cAMP-mediated signaling1 PublicationNAS:BHF-UCL
Cellular response to cAMPIDA:BHF-UCL
Cellular response to epinephrine stimulusIDA:BHF-UCL
Establishment of endothelial barrierISS:UniProtKB
Negative regulation of cAMP-mediated signalingManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of heart contractionBy SimilarityISS:BHF-UCL
Negative regulation of peptidyl-serine phosphorylationBy SimilarityISS:BHF-UCL
Negative regulation of relaxation of cardiac muscleISS:BHF-UCL
Positive regulation of interferon-gamma productionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of interleukin-2 productionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of interleukin-5 productionManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of cardiac muscle cell contractionBy SimilarityISS:BHF-UCL
Regulation of cell communication by electrical coupling involved in cardiac conduction1 PublicationIC:BHF-UCL
Regulation of heart rateBy SimilarityISS:BHF-UCL
Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulumBy SimilarityISS:BHF-UCL
Regulation of ryanodine-sensitive calcium-release channel activityBy SimilarityISS:BHF-UCL
Regulation of signaling receptor activityISS:BHF-UCL
Signal transductionManual Assertion Based On ExperimentIBA:GO_Central
T cell receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL

Cellular Location

Apical cell membrane
Cytoplasm
Membrane
Cytoplasm, cytoskeleton
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome (By similarity).
Colocalized with SHANK2 to the apical membrane of colonic crypt cells.

Involvement in disease

Acrodysostosis 2, with or without hormone resistance (ACRDYS2):
A pleiotropic disorder characterized by skeletal, endocrine, and neurological abnormalities. Skeletal features include brachycephaly, midface hypoplasia with a small upturned nose, brachydactyly, and lumbar spinal stenosis. Endocrine abnormalities include hypothyroidism and hypogonadism in males and irregular menses in females. Developmental disability is a common finding but is variable in severity and can be associated with significant behavioral problems.

PTM

Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through phosphorylation (By similarity).
Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.
Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.