high affinity cAMP-specific & IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B; HsPDE8B; cell proliferation-inducing gene 22 protein (PDE8B)

Function

• hydrolyzes the second messenger cAMP
• may be involved in specific signaling in the thyroid gland
• 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 (putative)

Inhibition:

• inhibited by dipyridimole
• insensitive to selective PDE inhibitors including rolipram & milrinone
• insensitibe 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 PAS (PER-ARNT-SIM) domain

Alternative splicing

named isoforms=6

Expression

• abundantly expressed in the thyroid
• low expression in brain, spinal cord & placenta
• in the thyroid gland isoform 1 predominates, & isoforms 2 & 6 are also highly expressed
• in the placenta, isoforms 1 & 2 are expressed equally
• in the brain, isoform 2 predominates

Pathology

• defects in PDE8B are the cause of striatal degeneration (autosomal dominant)

More general terms

• phosphodiesterase 8

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8622
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8622
• OMIM: https://mirror.omim.org/entry/603390
• OMIM: https://mirror.omim.org/entry/609161
• UniProt: http://www.uniprot.org/uniprot/O95263.html