cAMP-specific 3',5'-cyclic phosphodiesterase 4B

Details

Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4B
Synonyms
  • 3.1.4.53
  • DPDE4
  • PDE32
Gene Name
PDE4B
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000972|cAMP-specific 3',5'-cyclic phosphodiesterase 4B
MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQLPPLSQRQS
ERARTPEGDGISRPTTLPLTTLPSIAITTVSQECFDVENGPSPGRSPLDPQASSSAGLVL
HATFPGHSQRRESFLYRSDSDYDLSPKAMSRNSSLPSEQHGDDLIVTPFAQVLASLRSVR
NNFTILTNLHGTSNKRSPAASQPPVSRVNPQEESYQKLAMETLEELDWCLDQLETIQTYR
SVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLDKQNDVEIPSPTQKDREKKK
KQQLMTQISGVKKLMHSSSLNNTSISRFGVNTENEDHLAKELEDLNKWGLNIFNVAGYSH
NRPLTCIMYAIFQERDLLKTFRISSDTFITYMMTLEDHYHSDVAYHNSLHAADVAQSTHV
LLSTPALDAVFTDLEILAAIFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHL
AVGFKLLQEEHCDIFMNLTKKQRQTLRKMVIDMVLATDMSKHMSLLADLKTMVETKKVTS
SGVLLLDNYTDRIQVLRNMVHCADLSNPTKSLELYRQWTDRIMEEFFQQGDKERERGMEI
SPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVQPDAQDILDTLEDNRNWYQSMIPQSP
SPPLDEQNRDCQGLMEKFQFELTLDEEDSEGPEKEGEGHSYFSSTKTLCVIDPENRDSLG
ETDIDIATEDKSPVDT
Number of residues
736
Molecular Weight
83342.695
Theoretical pI
4.89
GO Classification
Functions
3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / ion channel binding / metal ion binding
Processes
cAMP catabolic process / cellular response to drug / cellular response to epinephrine stimulus / cellular response to lipopolysaccharide / leukocyte migration / negative regulation of relaxation of cardiac muscle / neutrophil chemotaxis / neutrophil homeostasis / positive regulation of interferon-gamma production / positive regulation of interleukin-2 production / regulation of cardiac muscle cell contraction / regulation of high voltage-gated calcium channel activity / T cell receptor signaling pathway
Components
cell periphery / centrosome / cytosol / dendritic spine / excitatory synapse / gamma-tubulin complex / membrane / postsynaptic density / synaptic vesicle / Z disc
General Function
Metal ion binding
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0016107|cAMP-specific 3',5'-cyclic phosphodiesterase 4B (PDE4B)
ATGAAGGAGCACGGGGGCACCTTCAGTAGCACCGGAATCAGCGGTGGTAGCGGTGACTCT
GCTATGGACAGCCTGCAGCCGCTCCAGCCTAACTACATGCCTGTGTGTTTGTTTGCAGAA
GAATCTTATCAAAAATTAGCAATGGAAACGCTGGAGGAATTAGACTGGTGTTTAGACCAG
CTAGAGACCATACAGACCTACCGGTCTGTCAGTGAGATGGCTTCTAACAAGTTCAAAAGA
ATGCTGAACCGGGAGCTGACACACCTCTCAGAGATGAGCCGATCAGGGAACCAGGTGTCT
GAATACATTTCAAATACTTTCTTAGACAAGCAGAATGATGTGGAGATCCCATCTCCTACC
CAGAAAGACAGGGAGAAAAAGAAAAAGCAGCAGCTCATGACCCAGATAAGTGGAGTGAAG
AAATTAATGCATAGTTCAAGCCTAAACAATACAAGCATCTCACGCTTTGGAGTCAACACT
GAAAATGAAGATCACCTGGCCAAGGAGCTGGAAGACCTGAACAAATGGGGTCTTAACATC
TTTAATGTGGCTGGATATTCTCACAATAGACCCCTAACATGCATCATGTATGCTATATTC
CAGGAAAGAGACCTCCTAAAGACATTCAGAATCTCATCTGACACATTTATAACCTACATG
ATGACTTTAGAAGACCATTACCATTCTGACGTGGCATATCACAACAGCCTGCACGCTGCT
GATGTAGCCCAGTCGACCCATGTTCTCCTTTCTACACCAGCATTAGACGCTGTCTTCACA
GATTTGGAGATCCTGGCTGCCATTTTTGCAGCTGCCATCCATGACGTTGATCATCCTGGA
GTCTCCAATCAGTTTCTCATCAACACAAATTCAGAACTTGCTTTGATGTATAATGATGAA
TCTGTGTTGGAAAATCATCACCTTGCTGTGGGTTTCAAACTGCTGCAAGAAGAACACTGT
GACATCTTCATGAATCTCACCAAGAAGCAGCGTCAGACACTCAGGAAGATGGTTATTGAC
ATGGTGTTAGCAACTGATATGTCTAAACATATGAGCCTGCTGGCAGACCTGAAGACAATG
GTAGAAACGAAGAAAGTTACAAGTTCAGGCGTTCTTCTCCTAGACAACTATACCGATCGC
ATTCAGGTCCTTCGCAACATGGTACACTGTGCAGACCTGAGCAACCCCACCAAGTCCTTG
GAATTGTATCGGCAATGGACAGACCGCATCATGGAGGAATTTTTCCAGCAGGGAGACAAA
GAGCGGGAGAGGGGAATGGAAATTAGCCCAATGTGTGATAAACACACAGCTTCTGTGGAA
AAATCCCAGGTTGGTTTCATCGACTACATTGTCCATCCATTGTGGGAGACATGGGCAGAT
TTGGTACAGCCTGATGCTCAGGACATTCTCGATACCTTAGAAGATAACAGGAACTGGTAT
CAGAGCATGATACCTCAAAGTCCCTCACCACCACTGGACGAGCAGAACAGGGACTGCCAG
GGTCTGATGGAGAAGTTTCAGTTTGAACTGACTCTCGATGAGGAAGATTCTGAAGGACCT
GAGAAGGAGGGAGAGGGACACAGCTATTTCAGCAGCACAAAGACGCTTTGTGTGATTGAT
CCAGAAAACAGAGATTCCCTGGGAGAGACTGACATAGACATTGCAACAGAAGACAAGTCC
CCCGTGGATACATAA
Chromosome Location
1
Locus
1p31
External Identifiers
ResourceLink
UniProtKB IDQ07343
UniProtKB Entry NamePDE4B_HUMAN
GenBank Protein ID347122
GenBank Gene IDL20966
GenAtlas IDPDE4B
HGNC IDHGNC:8781
General References
  1. Obernolte R, Bhakta S, Alvarez R, Bach C, Zuppan P, Mulkins M, Jarnagin K, Shelton ER: The cDNA of a human lymphocyte cyclic-AMP phosphodiesterase (PDE IV) reveals a multigene family. Gene. 1993 Jul 30;129(2):239-47. [PubMed:8392015]
  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. Cheung YF, Kan Z, Garrett-Engele P, Gall I, Murdoch H, Baillie GS, Camargo LM, Johnson JM, Houslay MD, Castle JC: PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4 variant whose isoform-specifying N-terminal region is identical to that of cAMP phosphodiesterase-4D6 (PDE4D6). J Pharmacol Exp Ther. 2007 Aug;322(2):600-9. Epub 2007 May 22. [PubMed:17519386]
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  7. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414]
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00651DyphyllineapprovedyesinhibitorDetails
DB00806Pentoxifyllineapproved, investigationalyesinhibitorDetails
DB00824Enprofyllineapproved, experimentalyesinhibitorDetails
DB01113Papaverineapproved, investigationalyesinhibitorDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB00277TheophyllineapprovedyesinhibitorDetails
DB01427AmrinoneapprovedunknowninhibitorDetails
DB01647DaxalipramexperimentalunknownDetails
DB00131Adenosine phosphateapproved, investigational, nutraceuticalunknownproduct ofDetails
DB01954RolipraminvestigationalunknownDetails
DB019593,5-Dimethyl-1-(3-Nitrophenyl)-1h-Pyrazole-4-Carboxylic Acid Ethyl EsterexperimentalunknownDetails
DB02660FilaminastexperimentalunknowninhibitorDetails
DB033498-Bromo-Adenosine-5'-MonophosphateexperimentalunknownDetails
DB03606(S)-RolipramexperimentalunknowninhibitorDetails
DB038071-(2-Chlorophenyl)-3,5-Dimethyl-1h-Pyrazole-4-Carboxylic Acid Ethyl EsterexperimentalunknownDetails
DB03849CilomilastinvestigationalyesinhibitorDetails
DB04149(R)-RolipramexperimentalunknowninhibitorDetails
DB04530S,S-(2-Hydroxyethyl)ThiocysteineexperimentalunknownDetails
DB01656RoflumilastapprovedunknowninhibitorDetails
DB05219Crisaboroleapproved, investigationalunknowninhibitorDetails
DB05676Apremilastapproved, investigationalyesantagonistDetails
DB01791PiclamilastexperimentalunknownDetails
DB01088Iloprostapproved, investigationalunknowninducerDetails
DB069091-ethyl-N-(phenylmethyl)-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideexperimentalunknownDetails
DB082994-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acidexperimentalunknownDetails
DB05266IbudilastinvestigationalyesinhibitorDetails
DB01412TheobromineinvestigationalunknowninhibitorDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB09283TrapidilexperimentalyesinhibitorDetails