high affinity cAMP-specific & IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A (PDE8A)

Function

• hydrolyzes the second messenger cAMP
• may be involved in maintaining basal levels of cAMP &/or in the cAMP regulation of germ cell development
• purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1

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 dipyridimole
• insensitive to selective PDE inhibitors including rolipram & zaprinast
• insensitive to the non-selective inhibitor, IBMX
• unaffected by cGMP

Structure

• composed of a C-terminal catalytic domain containing two putative divalent metal sites & an N-terminal regulatory domain
• belongs to the cyclic nucleotide phosphodiesterase family, PDE8 subfamily
• contains 1 PAC (PAS-associated C-terminal) domain
• contains 1 PAS (PER-ARNT-SIM) domain

Alternative splicing

named isoforms=4

Expression

• expressed in most tissues
• not expressed in thymus or peripheral blood leukocytes

highest expression in testis, ovary, small intestine & colon

More general terms

• phosphodiesterase 8

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5151
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5151
• OMIM: https://mirror.omim.org/entry/602972
• UniProt: http://www.uniprot.org/uniprot/O60658.html