cAMP-specific 3',5'-cyclic phosphodiesterase 4D; DPDE3; PDE43 (PDE4D, DPDE3)
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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 ,
- 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]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q08499.html
- ↑ Galoyan AA, Gurvitz BYa, Sharova NP. Cyclic nucleotide phosphodiesterase and 5'-nucleotidase: a coupled system. Neurochem Res. 1989 Dec;14(12):1213-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2560820
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17006457
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5144