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
- Functions3',5'-cyclic-AMP phosphodiesterase activity / cAMP binding / metal ion bindingProcessescAMP catabolic process / cellular response to drug / regulation of cAMP-mediated signaling / regulation of protein kinase A signaling / sensory perception of smell / signal transductionComponentscytosol / 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
- PDEase_I (PF00233)
- 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
Resource Link UniProtKB ID P27815 UniProtKB Entry Name PDE4A_HUMAN GenBank Protein ID 347120 GenBank Gene ID L20965 GenAtlas ID PDE4A HGNC ID HGNC:8780 - General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB00277 Theophylline approved yes inhibitor Details DB00824 Enprofylline approved, experimental yes inhibitor Details DB01088 Iloprost approved, investigational unknown inducer Details DB00975 Dipyridamole approved yes inhibitor Details DB00651 Dyphylline approved yes inhibitor Details DB05219 Crisaborole approved, investigational unknown inhibitor Details DB06479 Propentofylline investigational unknown Details DB05266 Ibudilast investigational yes inhibitor Details DB06751 Drotaverine approved, investigational yes inhibitor Details DB01791 Piclamilast experimental unknown Details DB06842 (4R)-4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one experimental unknown Details DB08299 4-[8-(3-nitrophenyl)-1,7-naphthyridin-6-yl]benzoic acid experimental unknown Details DB01303 Oxtriphylline approved yes inhibitor Details DB08811 Tofisopam experimental unknown inhibitor Details DB00201 Caffeine approved unknown inhibitor Details DB09283 Trapidil experimental yes inhibitor Details DB01427 Amrinone approved yes inhibitor Details DB01954 Rolipram investigational yes inhibitor Details DB01656 Roflumilast approved yes inhibitor Details