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cAMP-specific 3',5'-cyclic phosphodiesterase 4D; DPDE3; PDE43 (PDE4D, DPDE3)

Function: - hydrolyzes the second messenger cAMP - activated by phosphatidic acid - purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1 - isoform 3 & isoform 7 are activated by phosphorylation (in vitro) - isoform 6 is not activated by phosphorylation - isoform N3 & isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 & Ser-59 - isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B & AKAP9 - interacts with PDE4DIP - isoform 5, isoform N3 & isoform 12 bind GNB2L1 via their unique N-terminus - binds ARRB2 ,adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate , Cofactor: - binds 2 divalent metal cations per subunit - site 1 may preferentially bind Zn+2 - site 2 has a preference for Mg+2 &/or Mn+2 , Inhibition: - inhibited by rolipram. Structure: - homodimer for the long isoforms - isoforms with truncated N-termini are monomeric - belongs to the cyclic nucleotide phosphodiesterase family, PDE4 subfamily Compartment: - cytoplasm, membrane, cytoskeleton, centrosome (putative) - found in the soluble fraction, associated with membranes, & associated with the cytoskeleton & the centrosome (putative) Alternative splicing: - named isoforms=12 Expression: - widespread - most abundant in skeletal muscle - isoform 6 is detected in brain - isoform 8 is detected in brain, placenta, lung & kidney - isoform 7 is detected in heart & skeletal muscle Polymorphism: - genetic variations in PDE4D might (or might not) be associated with susceptibility to stroke [3]

General

phosphodiesterase 4; cAMP specific phosphodiesterase (PDE4)

Properties

SIZE: entity length = 809 aa MW = 91 kD COMPARTMENT: cytoplasm MOTIF: Ser phosphorylation site {S18} Ser phosphorylation site {S20} Thr phosphorylation site {T25} proline-rich region SITE: 42-88 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S190} Ser phosphorylation site {S197} Ser phosphorylation site {S202} Ser phosphorylation site {S348} cAMP-binding site SITE: 462-466 MOTIF: histidine residue {H462} cAMP-binding site SITE: 503-503 cAMP-binding site SITE: 620-620 asparagine residue {623} cAMP-binding site SITE: 671-671

Database Correlations

OMIM 600129 UniProt Q08499 Pfam PF00233 Entrez Gene 5144 Kegg hsa:5144 ENZYME 3.1.4.17

References

  1. UniProt :accession Q08499
  2. Galoyan AA, Gurvitz BYa, Sharova NP. Cyclic nucleotide phosphodiesterase and 5'-nucleotidase: a coupled system. Neurochem Res. 1989 Dec;14(12):1213-21. PMID: 2560820
  3. Rosand J et al Many hypotheses but no replication for the association between PDE4D and stroke. Nat Genet. 2003 Oct;35(2):131-8. PMID: 17006457
  4. Entrez Gene :accession 5144