cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
Details
- Name
- cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A
- Kind
- protein
- Synonyms
- 3.1.4.17
- cGI-PDE
- CGI-PDE A
- cGMP-inhibited cAMP phosphodiesterase
- Cyclic GMP-inhibited phosphodiesterase A
- Gene Name
- PDE3A
- UniProtKB Entry
- Q14432Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0021260|cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A MAVPGDAARVRDKPVHSGVSQAPTAGRDCHHRADPASPRDSGCRGCWGDLVLQPLRSSRK LSSALCAGSLSFLLALLVRLVRGEVGCDLEQCKEAAAAEEEEAAPGAEGGVFPGPRGGAP GGGARLSPWLQPSALLFSLLCAFFWMGLYLLRAGVRLPLAVALLAACCGGEALVQIGLGV GEDHLLSLPAAGVVLSCLAAATWLVLRLRLGVLMIALTSAVRTVSLISLERFKVAWRPYL AYLAGVLGILLARYVEQILPQSAEAAPREHLGSQLIAGTKEDIPVFKRRRRSSSVVSAEM SGCSSKSHRRTSLPCIPREQLMGHSEWDHKRGPRGSQSSGTSITVDIAVMGEAHGLITDL LADPSLPPNVCTSLRAVSNLLSTQLTFQAIHKPRVNPVTSLSENYTCSDSEESSEKDKLA IPKRLRRSLPPGLLRRVSSTWTTTTSATGLPTLEPAPVRRDRSTSIKLQEAPSSSPDSWN NPVMMTLTKSRSFTSSYAISAANHVKAKKQSRPGALAKISPLSSPCSSPLQGTPASSLVS KISAVQFPESADTTAKQSLGSHRALTYTQSAPDLSPQILTPPVICSSCGRPYSQGNPADE PLERSGVATRTPSRTDDTAQVTSDYETNNNSDSSDIVQNEDETECLREPLRKASACSTYA PETMMFLDKPILAPEPLVMDNLDSIMEQLNTWNFPIFDLVENIGRKCGRILSQVSYRLFE DMGLFEAFKIPIREFMNYFHALEIGYRDIPYHNRIHATDVLHAVWYLTTQPIPGLSTVIN DHGSTSDSDSDSGFTHGHMGYVFSKTYNVTDDKYGCLSGNIPALELMALYVAAAMHDYDH PGRTNAFLVATSAPQAVLYNDRSVLENHHAAAAWNLFMSRPEYNFLINLDHVEFKHFRFL VIEAILATDLKKHFDFVAKFNGKVNDDVGIDWTNENDRLLVCQMCIKLADINGPAKCKEL HLQWTDGIVNEFYEQGDEEASLGLPISPFMDRSAPQLANLQESFISHIVGPLCNSYDSAG LMPGKWVEDSDESGDTDDPEEEEEEAPAPNEEETCENNESPKKKTFKRRKIYCQITQHLL QNHKMWKKVIEEEQRLAGIENQSLDQTPQSHSSEQIQAIKEEEEEKGKPRGEEIPTQKPD Q
- Number of residues
- 1141
- Molecular Weight
- 124978.06
- Theoretical pI
- 5.87
- GO Classification
- Functions3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase activity / estrogen binding / nuclear estrogen receptor activityProcessesapoptotic signaling pathway / G protein-coupled receptor signaling pathway / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of cAMP-mediated signaling / regulation of ribonuclease activity / response to xenobiotic stimulusComponentsmembrane
- General Function
- Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099)
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Pfam Domain Function
- PDEase_I (PF00233)
- Signal Regions
- Not Available
- Transmembrane Regions
- 61-81 130-150 160-180 185-205 210-230 232-252
- Cellular Location
- Membrane
- Gene sequence
>lcl|BSEQ0021261|cGMP-inhibited 3',5'-cyclic phosphodiesterase A (PDE3A) ATGGCAGTGCCCGGCGACGCTGCACGAGTCAGGGACAAGCCCGTCCACAGTGGGGTGAGT CAAGCCCCCACGGCGGGCCGGGACTGCCACCATCGTGCGGACCCCGCATCGCCGCGGGAC TCGGGCTGCCGTGGCTGCTGGGGAGACCTGGTGCTGCAGCCGCTCCGGAGCTCTCGGAAA CTTTCCTCCGCGCTGTGCGCGGGCTCCCTGTCCTTTCTGCTGGCGCTGCTGGTGAGGCTG GTCCGCGGGGAGGTCGGCTGTGACCTGGAGCAGTGTAAGGAGGCGGCGGCGGCGGAGGAG GAGGAAGCAGCCCCGGGAGCAGAAGGGGGCGTCTTCCCGGGGCCTCGGGGAGGTGCTCCC GGGGGCGGTGCGCGGCTCAGCCCCTGGCTGCAGCCCTCGGCGCTGCTCTTCAGTCTCCTG TGTGCCTTCTTCTGGATGGGCTTGTACCTCCTGCGCGCCGGGGTGCGCCTGCCTCTGGCT GTCGCGCTGCTGGCCGCCTGCTGCGGGGGGGAAGCGCTCGTCCAGATTGGGCTGGGCGTC GGGGAGGATCACTTACTCTCACTCCCCGCCGCGGGGGTGGTGCTCAGCTGCTTGGCCGCC GCGACATGGCTGGTGCTGAGGCTGAGGCTGGGCGTCCTCATGATCGCCTTGACTAGCGCG GTCAGGACCGTGTCCCTCATTTCCTTAGAGAGGTTCAAGGTCGCCTGGAGACCTTACCTG GCGTACCTGGCCGGCGTGCTGGGGATCCTCTTGGCCAGGTACGTGGAACAAATCTTGCCG CAGTCCGCGGAGGCGGCTCCAAGGGAGCATTTGGGGTCCCAGCTGATTGCTGGGACCAAG GAAGATATCCCGGTGTTTAAGAGGAGGAGGCGGTCCAGCTCCGTCGTGTCCGCCGAGATG TCCGGCTGCAGCAGCAAGTCCCATCGGAGGACCTCCCTGCCCTGTATACCGAGGGAACAG CTCATGGGGCATTCAGAATGGGACCACAAACGAGGGCCAAGAGGATCACAGTCTTCAGGA ACCAGTATTACTGTGGACATCGCCGTCATGGGCGAGGCCCACGGCCTCATTACCGACCTC CTGGCAGACCCTTCTCTTCCACCAAACGTGTGCACATCCTTGAGAGCCGTGAGCAACTTG CTCAGCACACAGCTCACCTTCCAGGCCATTCACAAGCCCAGAGTGAATCCCGTCACTTCG CTCAGTGAAAACTATACCTGTTCTGACTCTGAAGAGAGCTCTGAAAAAGACAAGCTTGCT ATTCCAAAGCGCCTGAGAAGGAGTTTGCCTCCTGGCTTGTTGAGACGAGTTTCTTCCACT TGGACCACCACCACCTCGGCCACAGGTCTACCCACCTTGGAGCCTGCACCAGTACGGAGA GACCGCAGCACCAGCATCAAACTGCAGGAAGCACCTTCATCCAGTCCTGATTCTTGGAAT AATCCAGTGATGATGACCCTCACCAAAAGCAGATCCTTTACTTCATCCTATGCTATTTCT GCAGCTAACCATGTAAAGGCTAAAAAGCAAAGTCGACCAGGTGCCCTCGCTAAAATTTCA CCTCTTTCATCGCCCTGCTCCTCACCTCTCCAAGGGACTCCTGCCAGCAGCCTGGTCAGC AAAATTTCTGCAGTGCAGTTTCCAGAATCTGCTGACACAACTGCCAAACAAAGCCTAGGT TCTCACAGGGCCTTAACTTACACTCAGAGTGCCCCAGACCTATCCCCTCAAATCCTGACT CCACCTGTTATATGTAGCAGCTGTGGCAGACCATATTCCCAAGGGAATCCTGCTGATGAG CCCCTGGAGAGAAGTGGGGTAGCCACTCGGACACCAAGTAGAACAGATGACACTGCTCAA GTTACCTCTGATTATGAAACCAATAACAACAGTGACAGCAGTGACATTGTACAGAATGAA GATGAAACAGAGTGCCTGAGAGAGCCTCTGAGGAAAGCATCGGCTTGCAGCACCTATGCT CCTGAGACCATGATGTTTCTGGACAAACCAATTCTTGCTCCCGAACCTCTTGTCATGGAT AACCTGGACTCAATTATGGAGCAGCTAAATACTTGGAATTTTCCAATTTTTGATTTAGTG GAAAATATAGGAAGAAAATGTGGCCGTATTCTTAGTCAGGTATCTTACAGACTTTTTGAA GACATGGGCCTCTTTGAAGCTTTTAAAATTCCAATTAGGGAATTTATGAATTATTTTCAT GCTTTGGAGATTGGATATAGGGATATTCCTTATCATAACAGAATCCATGCCACTGATGTT TTACATGCTGTTTGGTATCTTACTACACAGCCTATTCCAGGCCTCTCAACTGTGATTAAT GATCATGGTTCAACCAGTGATTCAGATTCTGACAGTGGATTTACACATGGACATATGGGA TATGTATTCTCAAAAACGTATAATGTGACAGATGATAAATACGGATGTCTGTCTGGGAAT ATCCCTGCCTTGGAGTTGATGGCGCTGTATGTGGCTGCAGCCATGCACGATTATGATCAT CCAGGAAGGACTAATGCTTTCCTGGTTGCAACTAGTGCTCCTCAGGCGGTGCTATATAAC GATCGTTCAGTTTTGGAGAATCATCACGCAGCTGCTGCATGGAATCTTTTCATGTCCCGG CCAGAGTATAACTTCTTAATTAACCTTGACCATGTGGAATTTAAGCATTTCCGTTTCCTT GTCATTGAAGCAATTTTGGCCACTGACCTGAAGAAACACTTTGACTTCGTAGCCAAATTT AATGGCAAGGTAAATGATGATGTTGGAATAGATTGGACCAATGAAAATGATCGTCTACTG GTTTGTCAAATGTGTATAAAGTTGGCTGATATCAATGGTCCAGCTAAATGTAAAGAACTC CATCTTCAGTGGACAGATGGTATTGTCAATGAATTTTATGAACAGGGTGATGAAGAGGCC AGCCTTGGATTACCCATAAGCCCCTTCATGGATCGTTCTGCTCCTCAGCTGGCCAACCTT CAGGAATCCTTCATCTCTCACATTGTGGGGCCTCTGTGCAACTCCTATGATTCAGCAGGA CTAATGCCTGGAAAATGGGTGGAAGACAGCGATGAGTCAGGAGATACTGATGACCCAGAA GAAGAGGAGGAAGAAGCACCAGCACCAAATGAAGAGGAAACCTGTGAAAATAATGAATCT CCAAAAAAGAAGACTTTCAAAAGGAGAAAAATCTACTGCCAAATAACTCAGCACCTCTTA CAGAACCACAAGATGTGGAAGAAAGTCATTGAAGAGGAGCAACGGTTGGCAGGCATAGAA AATCAATCCCTGGACCAGACCCCTCAGTCGCACTCTTCAGAACAGATCCAGGCTATCAAG GAAGAAGAAGAAGAGAAAGGGAAACCAAGAGGCGAGGAGATACCAACCCAAAAGCCAGAC CAGTGA
- Chromosome Location
- 12
- Locus
- 12p12.2
- External Identifiers
Resource Link UniProtKB ID Q14432 UniProtKB Entry Name PDE3A_HUMAN GenBank Protein ID 38201493 GenBank Gene ID M91667 GeneCard ID PDE3A GenAtlas ID PDE3A HGNC ID HGNC:8778 PDB ID(s) 7EG0, 7EG1, 7EG4, 7KWE, 7L27, 7L28, 7L29, 7LRC, 7LRD KEGG ID hsa:5139 IUPHAR/Guide To Pharmacology ID 1298 NCBI Gene ID 5139 - General References
- Meacci E, Taira M, Moos M Jr, Smith CJ, Movsesian MA, Degerman E, Belfrage P, Manganiello V: Molecular cloning and expression of human myocardial cGMP-inhibited cAMP phosphodiesterase. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3721-5. [Article]
- Cheung PP, Xu H, McLaughlin MM, Ghazaleh FA, Livi GP, Colman RW: Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis. Blood. 1996 Aug 15;88(4):1321-9. [Article]
- Kuthe A, Eckel H, Stief CG, Uckert S, Forssmann WG, Jonas U, Magert HJ: Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum. Chem Biol Interact. 1999 May 14;119-120:593-8. [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]
- Degerman E, Moos M Jr, Rascon A, Vasta V, Meacci E, Smith CJ, Lindgren S, Andersson KE, Belfrage P, Manganiello V: Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase. Biochim Biophys Acta. 1994 Apr 13;1205(2):189-98. [Article]
- Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [Article]
- Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [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]
- Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
- Maass PG, Aydin A, Luft FC, Schachterle C, Weise A, Stricker S, Lindschau C, Vaegler M, Qadri F, Toka HR, Schulz H, Krawitz PM, Parkhomchuk D, Hecht J, Hollfinger I, Wefeld-Neuenfeld Y, Bartels-Klein E, Muhl A, Kann M, Schuster H, Chitayat D, Bialer MG, Wienker TF, Ott J, Rittscher K, Liehr T, Jordan J, Plessis G, Tank J, Mai K, Naraghi R, Hodge R, Hopp M, Hattenbach LO, Busjahn A, Rauch A, Vandeput F, Gong M, Ruschendorf F, Hubner N, Haller H, Mundlos S, Bilginturan N, Movsesian MA, Klussmann E, Toka O, Bahring S: PDE3A mutations cause autosomal dominant hypertension with brachydactyly. Nat Genet. 2015 Jun;47(6):647-53. doi: 10.1038/ng.3302. Epub 2015 May 11. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Anagrelide approved yes target inhibitor Details Theophylline approved yes target inhibitor Details Aminophylline approved yes target inhibitor Details Milrinone approved yes target inhibitor Details Amrinone approved yes target inhibitor Details Cilostazol approved, investigational yes target inhibitor Details Enoximone approved, investigational yes target inhibitor Details Levosimendan approved, investigational unknown target inhibitor Details Ibudilast investigational unknown target inhibitor Details Oxtriphylline approved yes target inhibitor Details Tofisopam experimental unknown target inhibitor Details 3-isobutyl-1-methyl-7H-xanthine experimental yes target inhibitor Details Vesnarinone investigational yes target inhibitor Details