PDE4A
Developmental stage
Isoform 2
Expressed in fetal brain.
Function
Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes.
Isoform 1
Efficiently hydrolyzes cAMP.
Isoform 2
Efficiently hydrolyzes cAMP.
Isoform 3
Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP.
Isoform 4
Efficiently hydrolyzes cAMP.
Isoform 6
Efficiently hydrolyzes cAMP.
Isoform 7
Efficiently hydrolyzes cAMP.
Pathway
Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1.
Post-translational modifications
Isoform 1
Proteolytically cleaved by CASP3.
Isoform 2
Phosphorylated at Ser-119 by PKA.
Sequence Similarities
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Tissue Specificity
Isoform 1
Expressed in lymphoid cell subsets including CD8-positive T cells and T-helper 2 cells. Expressed in dendritic cells.
Isoform 2
Highly expressed in liver, stomach, testis, thyroid and adrenal glands and at a lower extent in placenta, kidney, pancreas, ovary, uterus and skin. Expressed in myeloid cell subsets including dendritic cells, monocytes, macrophages, eosinophils and mast cells. Expressed in natural killer cells. Expressed in bronchial smooth muscle.
Isoform 6
Expressed at high levels in the heart and small intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood lymphocytes.
Isoform 7
Expressed predominantly in skeletal muscle and brain and at lower levels in the testis. Found in specific neuronal subpopulations including cortical pyramidal neurons, horn neurons in the spinal cord and Purkinje cells in cerebellum (at protein level).
Cellular localization
- Isoform 1
- Cytoplasm
- Perinuclear region
- Isoform 2
- Cytoplasm
- Perinuclear region
- Cell projection
- Ruffle membrane
- Isoform 3
- Cytoplasm
- Cytosol
- Isoform 4
- Membrane
- Peripheral membrane protein
- Isoform 4 has propensity for association with membranes.
- Isoform 6
- Cytoplasm
- Perinuclear region
- Isoform 7
- Cytoplasm
- Cytosol
- Membrane
- Peripheral membrane protein
- Predominantly cytosolic.
Alternative names
DPDE2, PDE4A, PDE46, cAMP-specific phosphodiesterase 4A