cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

Details

Name
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Synonyms
  • 3.1.4.17
Gene Name
PDE10A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001258|cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
MRIEERKSQHLTGLTDEKVKAYLSLHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAP
KEVSRYQDTNMQGVVYELNSYIEQRLDTGGDNQLLLYELSSIIKIATKADGFALYFLGEC
NNSLCIFTPPGIKEGKPRLIPAGPITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLE
SGTRIQSVLCLPIVTAIGDLIGILELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVC
RGLAKQTELNDFLLDVSKTYFDNIVAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELY
SDLFDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYT
GYTTRNILCMPIVSRGSVIGVVQMVNKISGSAFSKTDENNFKMFAVFCALALHCANMYHR
IRHSECIYRVTMEKLSYHSICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIF
VYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTD
LERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNI
FSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMM
TACDLCSVTKLWPVTKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFY
NAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRGEETATWISSPSVAQKAAASED
Number of residues
779
Molecular Weight
88411.71
Theoretical pI
6.57
GO Classification
Functions
3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase activity / cAMP binding / cGMP binding / cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / drug binding / metal ion binding
Processes
blood coagulation / cAMP catabolic process / cGMP catabolic process / regulation of cAMP-mediated signaling / regulation of protein kinase A signaling / signal transduction
Components
cytosol / membrane / perikaryon
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016160|cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A)
ATGGAAGATGGACCTTCTAATAATGCGAGCTGCTTCCGAAGGCTGACCGAGTGCTTCCTG
AGCCCCAGTTTGACAGATGAAAAAGTGAAGGCATATCTTTCTCTTCACCCCCAGGTATTA
GATGAATTTGTATCTGAAAGTGTTAGTGCAGAGACAGTAGAGAAATGGCTGAAGAGGAAG
AACAACAAATCAGAAGATGAATCAGCTCCTAAGGAAGTCAGCAGGTACCAAGATACGAAT
ATGCAGGGAGTTGTATATGAACTAAACAGCTATATAGAACAACGGTTGGACACAGGAGGA
GACAACCAGCTACTCCTCTATGAACTGAGCAGCATCATTAAAATAGCCACAAAAGCCGAT
GGATTTGCACTGTATTTCCTTGGAGAGTGCAATAATAGCCTGTGTATATTCACGCCACCT
GGGATAAAGGAAGGAAAACCCCGCCTCATCCCTGCTGGGCCCATCACTCAGGGCACCACC
GTCTCTGCTTATGTGGCCAAGTCCAGGAAAACACTGCTAGTAGAAGACATCCTTGGAGAT
GAACGATTTCCAAGAGGTACTGGACTGGAATCAGGGACTCGTATCCAGTCTGTTCTTTGC
TTACCAATTGTCACTGCAATTGGTGACTTGATTGGTATTCTCGAGCTGTATCGGCACTGG
GGCAAAGAAGCCTTCTGTCTTAGTCACCAGGAGGTTGCAACAGCAAATCTTGCCTGGGCT
TCAGTAGCAATACATCAGGTGCAGGTATGCAGAGGCCTTGCCAAACAGACAGAATTGAAT
GACTTCCTACTCGACGTATCAAAAACATATTTTGATAACATAGTTGCAATAGATTCTCTA
CTTGAACACATAATGATATATGCAAAAAACCTGGTGAATGCCGATCGTTGTGCGCTTTTC
CAGGTGGACCATAAGAACAAGGAGTTATATTCAGACCTTTTTGATATTGGAGAGGAAAAG
GAAGGAAAACCTGTCTTCAAGAAGACCAAAGAGATAAGATTTTCAATTGAGAAAGGAATT
GCTGGCCAAGTAGCAAGAACAGGGGAAGTCCTGAACATTCCAGATGCCTATGCAGACCCA
CGCTTTAACAGAGAAGTAGACTTGTACACAGGCTACACCACGCGGAACATCCTGTGCATG
CCCATCGTCAGCCGAGGCAGCGTGATAGGTGTGGTGCAGATGGTCAACAAAATCAGTGGC
AGTGCCTTCTCTAAAACAGATGAAAACAACTTCAAAATGTTTGCCGTCTTTTGTGCTTTA
GCCTTACACTGTGCTAATATGTATCATAGAATTCGCCACTCAGAGTGCATTTACCGGGTA
ACGATGGAAAAGCTGTCCTACCATAGCATTTGTACTTCAGAAGAGTGGCAAGGTCTCATG
CAATTCACCCTTCCCGTGCGTCTCTGCAAAGAAATTGAATTATTCCACTTTGACATTGGT
CCTTTTGAAAACATGTGGCCTGGAATTTTTGTCTACATGGTTCATCGGTCCTGTGGGACA
TCCTGCTTTGAGCTTGAAAAGTTGTGTCGTTTTATTATGTCTGTGAAGAAGAACTATCGG
CGGGTTCCTTATCACAACTGGAAGCATGCGGTCACTGTAGCACACTGCATGTATGCCATA
CTTCAGAACAATCACACGCTTTTCACAGACCTTGAGCGCAAAGGACTGCTGATTGCGTGT
CTGTGTCATGACCTGGACCACAGGGGCTTCAGTAACAGCTACCTGCAGAAGTTCGACCAC
CCTCTGGCCGCTCTCTACTCCACTTCCACCATGGAGCAGCACCACTTCTCCCAGACTGTG
TCCATCCTCCAGTTGGAAGGGCACAATATCTTCTCCACTCTGAGCTCCAGTGAATATGAG
CAGGTGCTTGAGATCATCCGCAAAGCCATCATTGCCACAGACCTTGCTTTATACTTTGGA
AACAGGAAGCAGTTGGAAGAGATGTACCAGACCGGATCACTAAACCTTAATAATCAATCA
CATAGAGACCGTGTAATTGGTTTGATGATGACTGCCTGTGACCTTTGTTCTGTGACAAAA
CTGTGGCCCGTTACAAAATTGACGGCAAATGATATATATGCAGAATTCTGGGCTGAGGGT
GATGAAATGAAGAAATTGGGAATACAGCCTATTCCTATGATGGACAGAGACAAGAAGGAT
GAAGTCCCCCAAGGCCAGCTTGGGTTCTACAATGCCGTGGCCATTCCCTGCTATACAACC
CTTACCCAGATCCTCCCTCCCACGGAGCCTCTTCTGAAAGCATGCAGGGATAATCTCAGT
CAGTGGGAGAAGGTGATTCGAGGGGAGGAGACTGCAACCTGGATTTCATCCCCATCCGTG
GCTCAGAAGGCAGCTGCATCTGAAGATTGA
Chromosome Location
6
Locus
6q26
External Identifiers
ResourceLink
UniProtKB IDQ9Y233
UniProtKB Entry NamePDE10_HUMAN
GenBank Protein ID4958858
GenBank Gene IDAB020593
GenAtlas IDPDE10A
HGNC IDHGNC:8772
General References
  1. Kotera J, Fujishige K, Yuasa K, Omori K: Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP. Biochem Biophys Res Commun. 1999 Aug 11;261(3):551-7. [PubMed:10441464]
  2. Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K: Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem. 1999 Jun 25;274(26):18438-45. [PubMed:10373451]
  3. Loughney K, Snyder PB, Uher L, Rosman GJ, Ferguson K, Florio VA: Isolation and characterization of PDE10A, a novel human 3', 5'-cyclic nucleotide phosphodiesterase. Gene. 1999 Jun 24;234(1):109-17. [PubMed:10393245]
  4. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed:14574404]
  5. 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]
  6. Fujishige K, Kotera J, Yuasa K, Omori K: The human phosphodiesterase PDE10A gene genomic organization and evolutionary relatedness with other PDEs containing GAF domains. Eur J Biochem. 2000 Oct;267(19):5943-51. [PubMed:10998054]
  7. Gross-Langenhoff M, Hofbauer K, Weber J, Schultz A, Schultz JE: cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11. J Biol Chem. 2006 Feb 3;281(5):2841-6. Epub 2005 Dec 5. [PubMed:16330539]
  8. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976]
  9. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195]
  10. Wang H, Liu Y, Hou J, Zheng M, Robinson H, Ke H: Structural insight into substrate specificity of phosphodiesterase 10. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5782-7. Epub 2007 Mar 26. [PubMed:17389385]
  11. Handa N, Mizohata E, Kishishita S, Toyama M, Morita S, Uchikubo-Kamo T, Akasaka R, Omori K, Kotera J, Terada T, Shirouzu M, Yokoyama S: Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP. J Biol Chem. 2008 Jul 11;283(28):19657-64. doi: 10.1074/jbc.M800595200. Epub 2008 May 13. [PubMed:18477562]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00975DipyridamoleapprovedyesinhibitorDetails
DB083834,5-bis(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazoleexperimentalunknownDetails
DB083842-({4-[4-(pyridin-4-ylmethyl)-1H-pyrazol-3-yl]phenoxy}methyl)quinolineexperimentalunknownDetails
DB083862-{[4-(4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinolineexperimentalunknownDetails
DB083872-{[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinolineexperimentalunknownDetails
DB083896,7-DIMETHOXY-4-[(3R)-3-(2-NAPHTHYLOXY)PYRROLIDIN-1-YL]QUINAZOLINEexperimentalunknownDetails
DB083916,7-DIMETHOXY-4-[(3R)-3-(QUINOXALIN-2-YLOXY)PYRROLIDIN-1-YL]QUINAZOLINEexperimentalunknownDetails
DB01113Papaverineapproved, investigationalunknowninhibitorDetails
DB08811TofisopamexperimentalunknowninhibitorDetails
DB08814Triflusalapproved, investigationalyesantagonistDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB09283TrapidilexperimentalyesinhibitorDetails