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Identification
HMDB Protein ID HMDBP00609
Secondary Accession Numbers
  • 5881
  • HMDBP04374
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Synonyms
  1. DPDE4
  2. PDE32
Gene Name PDE4B
Protein Type Unknown
Biological Properties
General Function Involved in catalytic activity
Specific Function Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Pathways
  • 3',5'-cyclic AMP degradation
  • Morphine addiction
  • Purine metabolism
Reactions
Adenosine 3',5'-cyclic phosphate + Water → Adenosine monophosphate details
Cyclic AMP + Water → Adenosine monophosphate details
Cyclic GMP + Water → Guanosine monophosphate details
GO Classification
Biological Process
signal transduction
cAMP catabolic process
Cellular Component
cytosol
perinuclear region of cytoplasm
nucleus
Function
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
cyclic-nucleotide phosphodiesterase activity
3',5'-cyclic-nucleotide phosphodiesterase activity
phosphoric ester hydrolase activity
phosphoric diester hydrolase activity
Molecular Function
metal ion binding
3',5'-cyclic-AMP phosphodiesterase activity
Process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
Cellular Location
  1. Cytoplasmic
Gene Properties
Chromosome Location 1
Locus 1p31
SNPs PDE4B
Gene Sequence
>2211 bp
ATGAAGAAAAGCAGGAGTGTGATGACGGTGATGGCTGATGATAATGTTAAAGATTATTTT
GAATGTAGCTTGAGTAAATCCTACAGTTCTTCCAGTAACACACTTGGGATCGACCTCTGG
AGAGGGAGAAGGTGTTGCTCAGGAAACTTACAGTTACCACCACTGTCTCAAAGACAGAGT
GAAAGGGCAAGGACTCCTGAGGGAGATGGTATTTCCAGGCCGACCACACTGCCTTTGACA
ACGCTTCCAAGCATTGCTATTACAACTGTAAGCCAGGAGTGCTTTGATGTGGAAAATGGC
CCTTCCCCAGGTCGGAGTCCACTGGATCCCCAGGCCAGCTCTTCCGCTGGGCTGGTACTT
CACGCCACCTTTCCTGGGCACAGCCAGCGCAGAGAGTCATTTCTCTACAGATCAGACAGC
GACTATGACTTGTCACCAAAGGCGATGTCGAGAAACTCTTCTCTTCCAAGCGAGCAACAC
GGCGATGACTTGATTGTAACTCCTTTTGCCCAGGTCCTTGCCAGCTTGCGAAGTGTGAGA
AACAACTTCACTATACTGACAAACCTTCATGGTACATCTAACAAGAGGTCCCCAGCTGCT
AGTCAGCCTCCTGTCTCCAGAGTCAACCCACAAGAAGAATCTTATCAAAAATTAGCAATG
GAAACGCTGGAGGAATTAGACTGGTGTTTAGACCAGCTAGAGACCATACAGACCTACCGG
TCTGTCAGTGAGATGGCTTCTAACAAGTTCAAAAGAATGCTGAACCGGGAGCTGACACAC
CTCTCAGAGATGAGCCGATCAGGGAACCAGGTGTCTGAATACATTTCAAATACTTTCTTA
GACAAGCAGAATGATGTGGAGATCCCATCTCCTACCCAGAAAGACAGGGAGAAAAAGAAA
AAGCAGCAGCTCATGACCCAGATAAGTGGAGTGAAGAAATTAATGCATAGTTCAAGCCTA
AACAATACAAGCATCTCACGCTTTGGAGTCAACACTGAAAATGAAGATCACCTGGCCAAG
GAGCTGGAAGACCTGAACAAATGGGGTCTTAACATCTTTAATGTGGCTGGATATTCTCAC
AATAGACCCCTAACATGCATCATGTATGCTATATTCCAGGAAAGAGACCTCCTAAAGACA
TTCAGAATCTCATCTGACACATTTATAACCTACATGATGACTTTAGAAGACCATTACCAT
TCTGACGTGGCATATCACAACAGCCTGCACGCTGCTGATGTAGCCCAGTCGACCCATGTT
CTCCTTTCTACACCAGCATTAGACGCTGTCTTCACAGATTTGGAGATCCTGGCTGCCATT
TTTGCAGCTGCCATCCATGACGTTGATCATCCTGGAGTCTCCAATCAGTTTCTCATCAAC
ACAAATTCAGAACTTGCTTTGATGTATAATGATGAATCTGTGTTGGAAAATCATCACCTT
GCTGTGGGTTTCAAACTGCTGCAAGAAGAACACTGTGACATCTTCATGAATCTCACCAAG
AAGCAGCGTCAGACACTCAGGAAGATGGTTATTGACATGGTGTTAGCAACTGATATGTCT
AAACATATGAGCCTGCTGGCAGACCTGAAGACAATGGTAGAAACGAAGAAAGTTACAAGT
TCAGGCGTTCTTCTCCTAGACAACTATACCGATCGCATTCAGGTCCTTCGCAACATGGTA
CACTGTGCAGACCTGAGCAACCCCACCAAGTCCTTGGAATTGTATCGGCAATGGACAGAC
CGCATCATGGAGGAATTTTTCCAGCAGGGAGACAAAGAGCGGGAGAGGGGAATGGAAATT
AGCCCAATGTGTGATAAACACACAGCTTCTGTGGAAAAATCCCAGGTTGGTTTCATCGAC
TACATTGTCCATCCATTGTGGGAGACATGGGCAGATTTGGTACAGCCTGATGCTCAGGAC
ATTCTCGATACCTTAGAAGATAACAGGAACTGGTATCAGAGCATGATACCTCAAAGTCCC
TCACCACCACTGGACGAGCAGAACAGGGACTGCCAGGGTCTGATGGAGAAGTTTCAGTTT
GAACTGACTCTCGATGAGGAAGATTCTGAAGGACCTGAGAAGGAGGGAGAGGGACACAGC
TATTTCAGCAGCACAAAGACGCTTTGTGTGATTGATCCAGAAAACAGAGATTCCCTGGGA
GAGACTGACATAGACATTGCAACAGAAGACAAGTCCCCCGTGGATACATAA
Protein Properties
Number of Residues 736
Molecular Weight 64351.765
Theoretical pI 4.916
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>cAMP-specific 3',5'-cyclic phosphodiesterase 4B
MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQLPPLSQRQS
ERARTPEGDGISRPTTLPLTTLPSIAITTVSQECFDVENGPSPGRSPLDPQASSSAGLVL
HATFPGHSQRRESFLYRSDSDYDLSPKAMSRNSSLPSEQHGDDLIVTPFAQVLASLRSVR
NNFTILTNLHGTSNKRSPAASQPPVSRVNPQEESYQKLAMETLEELDWCLDQLETIQTYR
SVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLDKQNDVEIPSPTQKDREKKK
KQQLMTQISGVKKLMHSSSLNNTSISRFGVNTENEDHLAKELEDLNKWGLNIFNVAGYSH
NRPLTCIMYAIFQERDLLKTFRISSDTFITYMMTLEDHYHSDVAYHNSLHAADVAQSTHV
LLSTPALDAVFTDLEILAAIFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHL
AVGFKLLQEEHCDIFMNLTKKQRQTLRKMVIDMVLATDMSKHMSLLADLKTMVETKKVTS
SGVLLLDNYTDRIQVLRNMVHCADLSNPTKSLELYRQWTDRIMEEFFQQGDKERERGMEI
SPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVQPDAQDILDTLEDNRNWYQSMIPQSP
SPPLDEQNRDCQGLMEKFQFELTLDEEDSEGPEKEGEGHSYFSSTKTLCVIDPENRDSLG
ETDIDIATEDKSPVDT
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q07343
UniProtKB/Swiss-Prot Entry Name PDE4B_HUMAN
PDB IDs
GenBank Gene ID L20966
GeneCard ID PDE4B
GenAtlas ID PDE4B
HGNC ID HGNC:8781
References
General References
  1. Zhang KY, Card GL, Suzuki Y, Artis DR, Fong D, Gillette S, Hsieh D, Neiman J, West BL, Zhang C, Milburn MV, Kim SH, Schlessinger J, Bollag G: A glutamine switch mechanism for nucleotide selectivity by phosphodiesterases. Mol Cell. 2004 Jul 23;15(2):279-86. [PubMed:15260978 ]
  2. Bolger G, Michaeli T, Martins T, St John T, Steiner B, Rodgers L, Riggs M, Wigler M, Ferguson K: A family of human phosphodiesterases homologous to the dunce learning and memory gene product of Drosophila melanogaster are potential targets for antidepressant drugs. Mol Cell Biol. 1993 Oct;13(10):6558-71. [PubMed:8413254 ]
  3. Huston E, Lumb S, Russell A, Catterall C, Ross AH, Steele MR, Bolger GB, Perry MJ, Owens RJ, Houslay MD: Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3. Biochem J. 1997 Dec 1;328 ( Pt 2):549-58. [PubMed:9371714 ]
  4. McLaughlin MM, Cieslinski LB, Burman M, Torphy TJ, Livi GP: A low-Km, rolipram-sensitive, cAMP-specific phosphodiesterase from human brain. Cloning and expression of cDNA, biochemical characterization of recombinant protein, and tissue distribution of mRNA. J Biol Chem. 1993 Mar 25;268(9):6470-6. [PubMed:8384210 ]
  5. Xu RX, Hassell AM, Vanderwall D, Lambert MH, Holmes WD, Luther MA, Rocque WJ, Milburn MV, Zhao Y, Ke H, Nolte RT: Atomic structure of PDE4: insights into phosphodiesterase mechanism and specificity. Science. 2000 Jun 9;288(5472):1822-5. [PubMed:10846163 ]
  6. Xu RX, Rocque WJ, Lambert MH, Vanderwall DE, Luther MA, Nolte RT: Crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP, 8-Br-AMP, and rolipram. J Mol Biol. 2004 Mar 19;337(2):355-65. [PubMed:15003452 ]
  7. Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY: Structural basis for the activity of drugs that inhibit phosphodiesterases. Structure. 2004 Dec;12(12):2233-47. [PubMed:15576036 ]
  8. Card GL, Blasdel L, England BP, Zhang C, Suzuki Y, Gillette S, Fong D, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY: A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat Biotechnol. 2005 Feb;23(2):201-7. Epub 2005 Jan 30. [PubMed:15685167 ]
  9. Wang H, Peng MS, Chen Y, Geng J, Robinson H, Houslay MD, Cai J, Ke H: Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors. Biochem J. 2007 Dec 1;408(2):193-201. [PubMed:17727341 ]
  10. Hamblin JN, Angell TD, Ballantine SP, Cook CM, Cooper AW, Dawson J, Delves CJ, Jones PS, Lindvall M, Lucas FS, Mitchell CJ, Neu MY, Ranshaw LE, Solanke YE, Somers DO, Wiseman JO: Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors. Bioorg Med Chem Lett. 2008 Jul 15;18(14):4237-41. doi: 10.1016/j.bmcl.2008.05.052. Epub 2008 May 17. [PubMed:18539455 ]