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

Details

Name
cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Synonyms
  • 3.1.4.53
  • DPDE2
  • PDE46
Gene Name
PDE4A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002254|cAMP-specific 3',5'-cyclic phosphodiesterase 4A
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR
SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP
FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW
CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI
PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD
QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML
TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV
SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM
VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE
LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL
VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE
ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT
QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP
STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
Number of residues
886
Molecular Weight
98142.155
Theoretical pI
4.87
GO Classification
Functions
3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / metal ion binding
Processes
cAMP catabolic process / cellular response to drug / regulation of cAMP-mediated signaling / regulation of protein kinase A signaling / sensory perception of smell / signal transduction
Components
cytosol / membrane / perinuclear region of cytoplasm / ruffle membrane
General Function
Metal ion binding
Specific Function
Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016323|cAMP-specific 3',5'-cyclic phosphodiesterase 4A (PDE4A)
ATGGAACCCCCGACCGTCCCCTCGGAAAGGAGCCTGTCTCTGTCACTGCCCGGGCCCCGG
GAGGGCCAGGCCACCCTGAAGCCTCCCCCGCAGCACCTGTGGCGGCAGCCTCGGACCCCC
ATCCGTATCCAGCAGCGCGGCTACTCCGACAGCGCGGAGCGCGCCGAGCGGGAGCGGCAG
CCGCACCGGCCCATAGAGCGCGCCGATGCCATGGACACCAGCGACCGGCCCGGCCTGCGC
ACGACCCGCATGTCCTGGCCCTCGTCCTTCCATGGCACTGGCACCGGCAGCGGCGGCGCG
GGCGGAGGCAGCAGCAGGCGCTTCGAGGCAGAGAATGGGCCGACACCATCTCCTGGCCGC
AGCCCCCTGGACTCGCAGGCGAGCCCAGGACTCGTGCTGCACGCCGGGGCGGCCACCAGC
CAGCGCCGGGAGTCCTTCCTGTACCGCTCAGACAGCGACTATGACATGTCACCCAAGACC
ATGTCCCGGAACTCATCGGTCACCAGCGAGGCGCACGCTGAAGACCTCATCGTAACACCA
TTTGCTCAGGTGCTGGCCAGCCTCCGGAGCGTCCGTAGCAACTTCTCACTCCTGACCAAT
GTGCCCGTTCCCAGTAACAAGCGGTCCCCGCTGGGCGGCCCCACCCCTGTCTGCAAGGCC
ACGCTGTCAGAAGAAACGTGTCAGCAGTTGGCCCGGGAGACTCTGGAGGAGCTGGACTGG
TGTCTGGAGCAGCTGGAGACCATGCAGACCTATCGCTCTGTCAGCGAGATGGCCTCGCAC
AAGTTCAAAAGGATGTTGAACCGTGAGCTCACACACCTGTCAGAAATGAGCAGGTCCGGA
AACCAGGTCTCAGAGTACATTTCCACAACATTCCTGGACAAACAGAATGAAGTGGAGATC
CCATCACCCACGATGAAGGAACGAGAAAAACAGCAAGCGCCGCGACCAAGACCCTCCCAG
CCGCCCCCGCCCCCTGTACCACACTTACAGCCCATGTCCCAAATCACAGGGTTGAAAAAG
TTGATGCATAGTAACAGCCTGAACAACTCTAACATTCCCCGATTTGGGGTGAAGACCGAT
CAAGAAGAGCTCCTGGCCCAAGAACTGGAGAACCTGAACAAGTGGGGCCTGAACATCTTT
TGCGTGTCGGATTACGCTGGAGGCCGCTCACTCACCTGCATCATGTACATGATATTCCAG
GAGCGGGACCTGCTGAAGAAATTCCGCATCCCTGTGGACACGATGGTGACATACATGCTG
ACGCTGGAGGATCACTACCACGCTGACGTGGCCTACCATAACAGCCTGCACGCAGCTGAC
GTGCTGCAGTCCACCCACGTACTGCTGGCCACGCCTGCACTAGATGCAGTGTTCACGGAC
CTGGAGATTCTCGCCGCCCTCTTCGCGGCTGCCATCCACGATGTGGATCACCCTGGGGTC
TCCAACCAGTTCCTCATCAACACCAATTCGGAGCTGGCGCTCATGTACAACGATGAGTCG
GTGCTCGAGAATCACCACCTGGCCGTGGGCTTCAAGCTGCTGCAGGAGGACAACTGCGAC
ATCTTCCAGAACCTCAGCAAGCGCCAGCGGCAGAGCCTACGCAAGATGGTCATCGACATG
GTGCTGGCCACGGACATGTCCAAGCACATGACCCTCCTGGCTGACCTGAAGACCATGGTG
GAGACCAAGAAAGTGACCAGCTCAGGGGTCCTCCTGCTAGATAACTACTCCGACCGCATC
CAGGTCCTCCGGAACATGGTGCACTGTGCCGACCTCAGCAACCCCACCAAGCCGCTGGAG
CTGTACCGCCAGTGGACAGACCGCATCATGGCCGAGTTCTTCCAGCAGGGTGACCGAGAG
CGCGAGCGTGGCATGGAAATCAGCCCCATGTGTGACAAGCACACTGCCTCCGTGGAGAAG
TCTCAGGTGGGTTTTATTGACTACATTGTGCACCCATTGTGGGAGACCTGGGCGGACCTT
GTCCACCCAGATGCCCAGGAGATCTTGGACACTTTGGAGGACAACCGGGACTGGTACTAC
AGCGCCATCCGGCAGAGCCCATCTCCGCCACCCGAGGAGGAGTCAAGGGGGCCAGGCCAC
CCACCCCTGCCTGACAAGTTCCAGTTTGAGCTGACGCTGGAGGAGGAAGAGGAGGAAGAA
ATATCAATGGCCCAGATACCGTGCACAGCCCAAGAGGCATTGACTGCGCAGGGATTGTCA
GGAGTCGAGGAAGCTCTGGATGCAACCATAGCCTGGGAGGCATCCCCGGCCCAGGAGTCG
TTGGAAGTTATGGCACAGGAAGCATCCCTGGAGGCCGAGCTGGAGGCAGTGTATTTGACA
CAGCAGGCACAGTCCACAGGCAGTGCACCTGTGGCTCCGGATGAGTTCTCGTCCCGGGAG
GAATTCGTGGTTGCTGTAAGCCACAGCAGCCCCTCTGCCCTGGCTCTTCAAAGCCCCCTT
CTCCCTGCTTGGAGGACCCTGTCTGTTTCAGAGCATGCCCCGGGCCTCCCGGGCCTCCCC
TCCACGGCGGCCGAGGTGGAGGCCCAACGAGAGCACCAGGCTGCCAAGAGGGCTTGCAGT
GCCTGCGCAGGGACATTTGGGGAGGACACATCCGCACTCCCAGCTCCTGGTGGCGGGGGG
TCAGGTGGAGACCCTACCTGA
Chromosome Location
19
Locus
19p13.2
External Identifiers
ResourceLink
UniProtKB IDP27815
UniProtKB Entry NamePDE4A_HUMAN
GenBank Protein ID347120
GenBank Gene IDL20965
GenAtlas IDPDE4A
HGNC IDHGNC:8780
General References
  1. 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]
  2. Sullivan M, Egerton M, Shakur Y, Marquardsen A, Houslay MD: Molecular cloning and expression, in both COS-1 cells and S. cerevisiae, of a human cytosolic type-IVA, cyclic AMP specific phosphodiesterase (hPDE-IVA-h6.1). Cell Signal. 1994 Sep;6(7):793-812. [PubMed:7888306]
  3. Horton YM, Sullivan M, Houslay MD: Molecular cloning of a novel splice variant of human type IVA (PDE-IVA) cyclic AMP phosphodiesterase and localization of the gene to the p13.2-q12 region of human chromosome 19 [corrected]. Biochem J. 1995 Jun 1;308 ( Pt 2):683-91. [PubMed:7772058]
  4. Sullivan M, Rena G, Begg F, Gordon L, Olsen AS, Houslay MD: Identification and characterization of the human homologue of the short PDE4A cAMP-specific phosphodiesterase RD1 (PDE4A1) by analysis of the human HSPDE4A gene locus located at chromosome 19p13.2. Biochem J. 1998 Aug 1;333 ( Pt 3):693-703. [PubMed:9677330]
  5. Rena G, Begg F, Ross A, MacKenzie C, McPhee I, Campbell L, Huston E, Sullivan M, Houslay MD: Molecular cloning, genomic positioning, promoter identification, and characterization of the novel cyclic amp-specific phosphodiesterase PDE4A10. Mol Pharmacol. 2001 May;59(5):996-1011. [PubMed:11306681]
  6. Wallace DA, Johnston LA, Huston E, MacMaster D, Houslay TM, Cheung YF, Campbell L, Millen JE, Smith RA, Gall I, Knowles RG, Sullivan M, Houslay MD: Identification and characterization of PDE4A11, a novel, widely expressed long isoform encoded by the human PDE4A cAMP phosphodiesterase gene. Mol Pharmacol. 2005 Jun;67(6):1920-34. Epub 2005 Feb 28. [PubMed:15738310]
  7. Mackenzie KF, Topping EC, Bugaj-Gaweda B, Deng C, Cheung YF, Olsen AE, Stockard CR, High Mitchell L, Baillie GS, Grizzle WE, De Vivo M, Houslay MD, Wang D, Bolger GB: Human PDE4A8, a novel brain-expressed PDE4 cAMP-specific phosphodiesterase that has undergone rapid evolutionary change. Biochem J. 2008 Apr 15;411(2):361-9. [PubMed:18095939]
  8. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. [PubMed:15057824]
  9. 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]
  10. Livi GP, Kmetz P, McHale MM, Cieslinski LB, Sathe GM, Taylor DP, Davis RL, Torphy TJ, Balcarek JM: Cloning and expression of cDNA for a human low-Km, rolipram-sensitive cyclic AMP phosphodiesterase. Mol Cell Biol. 1990 Jun;10(6):2678-86. [PubMed:2160582]
  11. Lario PI, Bobechko B, Bateman K, Kelly J, Vrielink A, Huang Z: Purification and characterization of the human PDE4A catalytic domain (PDE4A330-723) expressed in Sf9 cells. Arch Biochem Biophys. 2001 Oct 1;394(1):54-60. [PubMed:11566027]
  12. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258]
  13. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  14. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332]
  15. Li X, Vadrevu S, Dunlop A, Day J, Advant N, Troeger J, Klussmann E, Jaffrey E, Hay RT, Adams DR, Houslay MD, Baillie GS: Selective SUMO modification of cAMP-specific phosphodiesterase-4D5 (PDE4D5) regulates the functional consequences of phosphorylation by PKA and ERK. Biochem J. 2010 Apr 28;428(1):55-65. doi: 10.1042/BJ20091672. [PubMed:20196770]
  16. 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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00277TheophyllineapprovedyesinhibitorDetails
DB00824Enprofyllineapproved, experimentalyesinhibitorDetails
DB01088Iloprostapproved, investigationalunknowninducerDetails
DB00975DipyridamoleapprovedyesinhibitorDetails
DB00806Pentoxifyllineapproved, investigationalyesinhibitorDetails
DB00651DyphyllineapprovedyesinhibitorDetails
DB01656RoflumilastapprovedunknowninhibitorDetails
DB05219Crisaboroleapproved, investigationalunknowninhibitorDetails
DB06479PropentofyllineinvestigationalunknownDetails
DB05266IbudilastinvestigationalyesinhibitorDetails
DB06751Drotaverineapproved, investigationalyesinhibitorDetails
DB01791PiclamilastexperimentalunknownDetails
DB06842(4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-oneexperimentalunknownDetails
DB082994-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acidexperimentalunknownDetails
DB01303OxtriphyllineapprovedyesinhibitorDetails
DB08811TofisopamexperimentalunknowninhibitorDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB09283TrapidilexperimentalyesinhibitorDetails