PDE4D
Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Involvement in disease
Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Post-translational modifications
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.
Sequence Similarities
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Tissue Specificity
Expressed in colonic epithelial cells (at protein level). Widespread; most abundant in skeletal muscle.
Isoform 6
Detected in brain.
Isoform 8
Detected in brain, placenta, lung and kidney.
Isoform 7
Detected in heart and skeletal muscle.
Cellular localization
- 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.
Alternative names
DPDE3, PDE4D, PDE43, cAMP-specific phosphodiesterase 4D