cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
Details
- Name
- cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
- Kind
- protein
- Synonyms
- 3.1.4.17
- Gene Name
- PDE10A
- UniProtKB Entry
- Q9Y233Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0063893|cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A MASLEEPLAPRPQGPLPAAGDEPGCGPGKLRPEPRLSAAGGGSAAGPGPAPEWPGRGRAE RAAPPRPPLSSAGRPSPAGGPGALSARGGGCGWVAARAPLALAFSSRVPSSSPSFFYFWP PPPPPPPSFLPSSSAFHLPVRLPGREGAAAAAAAGGGGDAGGGGGGGQEAAPLSVPTSSS HRGGGGSGGGRRRLFLSPALQGLLLPARAGPRPPPPPRLPLGQAARRAGSPGFPGAGPGG GGQTPRRPQGASFALAAAAALLFGSDMEDGPSNNASCFRRLTECFLSPSLTDEKVKAYLS LHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAPKEVSRYQDTNMQGVVYELNSYIEQ RLDTGGDNQLLLYELSSIIKIATKADGFALYFLGECNNSLCIFTPPGIKEGKPRLIPAGP ITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLESGTRIQSVLCLPIVTAIGDLIGIL ELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVCRGLAKQTELNDFLLDVSKTYFDNI VAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELYSDLFDIGEEKEGKPVFKKTKEIRF SIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYTGYTTRNILCMPIVSRGSVIGVVQM VNKISGSAFSKTDENNFKMFAVFCALALHCANMYHRIRHSECIYRVTMEKLSYHSICTSE EWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIFVYMVHRSCGTSCFELEKLCRFIMS VKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTDLERKGLLIACLCHDLDHRGFSNSY LQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNIFSTLSSSEYEQVLEIIRKAIIATD LALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMMTACDLCSVTKLWPVTKLTANDIYA EFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFYNAVAIPCYTTLTQILPPTEPLLKA CRDNLSQWEKVIRGEETATWISSPSVAQKAAASED
- Number of residues
- 1055
- Molecular Weight
- 114945.16
- Theoretical pI
- 6.57
- GO Classification
- Functions3',5'-cyclic-AMP phosphodiesterase activityProcessescAMP-mediated signaling / negative regulation of cGMP-mediated signaling
- General Function
- Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10373451, PubMed:10393245, PubMed:16330539, PubMed:17389385, PubMed:27058447). Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10373451, PubMed:10393245, PubMed:17389385, PubMed:27058447). May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:27058447)
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm, cytosol
- 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
- 6q27
- External Identifiers
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [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]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Dipyridamole approved yes target inhibitor Details 4,5-bis(4-methoxyphenyl)-2-thiophen-2-yl-1H-imidazole experimental unknown target Details 2-({4-[4-(pyridin-4-ylmethyl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline experimental unknown target Details 2-{[4-(4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinoline experimental unknown target Details Mardepodect investigational yes target inhibitor Details 6,7-DIMETHOXY-4-[(3R)-3-(2-NAPHTHYLOXY)PYRROLIDIN-1-YL]QUINAZOLINE experimental unknown target Details PQ-10 experimental unknown target Details Papaverine approved, investigational unknown target inhibitor Details Tofisopam experimental yes target inhibitor Details Triflusal approved, investigational yes target antagonist Details Balipodect investigational yes target inhibitor Details