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Identification
HMDB Protein ID HMDBP00650
Secondary Accession Numbers
  • 5922
  • HMDBP04378
Name cAMP-specific 3',5'-cyclic phosphodiesterase 4A
Synonyms
  1. DPDE2
  2. PDE46
Gene Name PDE4A
Protein Type Unknown
Biological Properties
General Function Involved in 3',5'-cyclic-nucleotide phosphodiesterase activity
Specific Function Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
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
response to drug
cAMP catabolic process
Cellular Component
cytosol
perinuclear region of cytoplasm
nucleus
ruffle membrane
membrane
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. Membrane
  2. Isoform 7:Cytoplasm
Gene Properties
Chromosome Location 19
Locus 19p13.2
SNPs PDE4A
Gene Sequence
>2661 bp
ATGGAACCCCCGACCGTCCCCTCGGAAAGGAGCCTGTCTCTGTCACTGCCCGGGCCCCGG
GAGGGCCAGGCCACCCTGAAGCCTCCCCCGCAGCACCTGTGGCGGCAGCCTCGGACCCCC
ATCCGTATCCAGCAGCGCGGCTACTCCGACAGCGCGGAGCGCGCCGAGCGGGAGCGGCAG
CCGCACCGGCCCATAGAGCGCGCCGATGCCATGGACACCAGCGACCGGCCCGGCCTGCGC
ACGACCCGCATGTCCTGGCCCTCGTCCTTCCATGGCACTGGCACCGGCAGCGGCGGCGCG
GGCGGAGGCAGCAGCAGGCGCTTCGAGGCAGAGAATGGGCCGACACCATCTCCTGGCCGC
AGCCCCCTGGACTCGCAGGCGAGCCCAGGACTCGTGCTGCACGCCGGGGCGGCCACCAGC
CAGCGCCGGGAGTCCTTCCTGTACCGCTCAGACAGCGACTATGACATGTCACCCAAGACC
ATGTCCCGGAACTCATCGGTCACCAGCGAGGCGCACGCTGAAGACCTCATCGTAACACCA
TTTGCTCAGGTGCTGGCCAGCCTCCGGAGCGTCCGTAGCAACTTCTCACTCCTGACCAAT
GTGCCCGTTCCCAGTAACAAGCGGTCCCCGCTGGGCGGCCCCACCCCTGTCTGCAAGGCC
ACGCTGTCAGAAGAAACGTGTCAGCAGTTGGCCCGGGAGACTCTGGAGGAGCTGGACTGG
TGTCTGGAGCAGCTGGAGACCATGCAGACCTATCGCTCTGTCAGCGAGATGGCCTCGCAC
AAGTTCAAAAGGATGTTGAACCGTGAGCTCACACACCTGTCAGAAATGAGCAGGTCCGGA
AACCAGGTCTCAGAGTACATTTCCACAACATTCCTGGACAAACAGAATGAAGTGGAGATC
CCATCACCCACGATGAAGGAACGAGAAAAACAGCAAGCGCCGCGACCAAGACCCTCCCAG
CCGCCCCCGCCCCCTGTACCACACTTACAGCCCATGTCCCAAATCACAGGGTTGAAAAAG
TTGATGCATAGTAACAGCCTGAACAACTCTAACATTCCCCGATTTGGGGTGAAGACCGAT
CAAGAAGAGCTCCTGGCCCAAGAACTGGAGAACCTGAACAAGTGGGGCCTGAACATCTTT
TGCGTGTCGGATTACGCTGGAGGCCGCTCACTCACCTGCATCATGTACATGATATTCCAG
GAGCGGGACCTGCTGAAGAAATTCCGCATCCCGGTGGACACGATGGTGACATACATGCTG
ACGCTGGAGGATCACTACCACGCTGACGTGGCCTACCATAACAGCCTGCACGCAGCTGAC
GTGCTGCAGTCCACCCACGTACTGCTGGCCACGCCTGCACTAGATGCAGTGTTCACGGAC
CTGGAGATTCTCGCCGCCCTCTTCGCGGCTGCCATCCACGATGTGGATCACCCTGGGGTC
TCCAACCAGTTCCTCATCAACACCAATTCGGAGCTGGCGCTCATGTACAACGATGAGTCG
GTGCTCGAGAATCACCACCTGGCCGTGGGCTTCAAGCTGCTGCAGGAGGACAACTGCGAC
ATCTTCCAGAACCTCAGCAAGCGCCAGCGGCAGAGCCTACGCAAGATGGTCATCGACATG
GTGCTGGCCACGGACATGTCCAAGCACATGACCCTCCTGGCTGACCTGAAGACCATGGTG
GAGACCAAGAAAGTGACCAGCTCAGGGGTCCTCCTGCTAGATAACTACTCCGACCGCATC
CAGGTCCTCCGGAACATGGTGCACTGTGCCGACCTCAGCAACCCCACCAAGCCGCTGGAG
CTGTACCGCCAGTGGACAGACCGCATCATGGCCGAGTTCTTCCAGCAGGGTGACCGAGAG
CGCGAGCGTGGCATGGAAATCAGCCCCATGTGTGACAAGCACACTGCCTCCGTGGAGAAG
TCTCAGGTGGGTTTTATTGACTACATTGTGCACCCATTGTGGGAGACCTGGGCGGACCTT
GTCCACCCAGATGCCCAGGAGATCTTGGACACTTTGGAGGACAACCGGGACTGGTACTAC
AGCGCCATCCGGCAGAGCCCATCTCCGCCACCCGAGGAGGAGTCAAGGGGGCCAGGCCAC
CCACCCCTGCCTGACAAGTTCCAGTTTGAGCTGACGCTGGAGGAGGAAGAGGAGGAAGAA
ATATCAATGGCCCAGATACCGTGCACAGCCCAAGAGGCATTGACTGCGCAGGGATTGTCA
GGAGTCGAGGAAGCTCTGGATGCAACCATAGCCTGGGAGGCATCCCCGGCCCAGGAGTCG
TTGGAAGTTATGGCACAGGAAGCATCCCTGGAGGCCGAGCTGGAGGCAGTGTATTTGACA
CAGCAGGCACAGTCCACAGGCAGTGCACCTGTGGCTCCGGATGAGTTCTCGTCCCGGGAG
GAATTCGTGGTTGCTGTAAGCCACAGCAGCCCCTCTGCCCTGGCTCTTCAAAGCCCCCTT
CTCCCTGCTTGGAGGACCCTGTCTGTTTCAGAGCATGCCCCGGGCCTCCCGGGCCTCCCC
TCCACGGCGGCCGAGGTGGAGGCCCAACGAGAGCACCAGGCTGCCAAGAGGGCTTGCAGT
GCCTGCGCAGGGACATTTGGGGAGGACACATCCGCACTCCCAGCTCCTGGTGGCGGGGGG
TCAGGTGGAGACCCTACCTGA
Protein Properties
Number of Residues 886
Molecular Weight 98142.155
Theoretical pI 5.211
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>cAMP-specific 3',5'-cyclic phosphodiesterase 4A
MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR
SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP
FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW
CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI
PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD
QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML
TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV
SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM
VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE
LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL
VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE
ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT
QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP
STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P27815
UniProtKB/Swiss-Prot Entry Name PDE4A_HUMAN
PDB IDs
GenBank Gene ID L20965
GeneCard ID PDE4A
GenAtlas ID PDE4A
HGNC ID HGNC:8780
References
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [PubMed:14759258 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]