ID:PDE4D_HUMAN DESCRIPTION: RecName: Full=cAMP-specific 3',5'-cyclic phosphodiesterase 4D; EC=3.1.4.17; AltName: Full=DPDE3; AltName: Full=PDE43; FUNCTION: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. CATALYTIC ACTIVITY: Adenosine 3',5'-cyclic phosphate + H(2)O = adenosine 5'-phosphate. COFACTOR: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. ENZYME REGULATION: Inhibited by rolipram. Activated by phosphatidic acid. PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1. SUBUNIT: Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Isoform 5, isoform N3 and isoform 12 bind GNB2L1 via their unique N-terminus. Binds ARRB2. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Membrane (By similarity). Cytoplasm, cytoskeleton (By similarity). Cytoplasm, cytoskeleton, centrosome (By similarity). Note=Found in the soluble fraction, associated with membranes, and associated with the cytoskeleton and the centrosome (By similarity). TISSUE SPECIFICITY: Widespread; most abundant in skeletal muscle. Isoform 6 is detected in brain. Isoform 8 is detected in brain, placenta, lung and kidney. Isoform 7 is detected in heart and skeletal muscle. PTM: 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. PTM: Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation. DISEASE: Note=Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution. DISEASE: Defects in PDE4D are the cause of acrodysostosis type 2, with or without hormone resistance (ACRDYS2) [MIM:614613]. ACRDYS2 is 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. SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q08499
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
