cGMP-specific 3',5'-cyclic phosphodiesterase

Details

Name
cGMP-specific 3',5'-cyclic phosphodiesterase
Synonyms
  • 3.1.4.35
  • CGB-PDE
  • cGMP-binding cGMP-specific phosphodiesterase
  • PDE5
Gene Name
PDE5A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036966|cGMP-specific 3',5'-cyclic phosphodiesterase
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAE
RVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEG
TVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLI
SADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPL
NIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDE
KDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIIS
FMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTME
PLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGK
VKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETREL
QSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWIL
SVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGV
NNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAI
LATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAE
LVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCF
PLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
Number of residues
875
Molecular Weight
99984.14
Theoretical pI
6.0
GO Classification
Functions
3',5'-cyclic-GMP phosphodiesterase activity / 3',5'-cyclic-nucleotide phosphodiesterase activity / cGMP binding / metal ion binding
Processes
blood coagulation / cGMP catabolic process / negative regulation of cardiac muscle contraction / negative regulation of T cell proliferation / positive regulation of cardiac muscle hypertrophy / positive regulation of MAP kinase activity / positive regulation of oocyte development / regulation of cGMP metabolic process / relaxation of cardiac muscle / signal transduction
Components
cytosol
General Function
Metal ion binding
Specific Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0009989|cGMP-specific 3',5'-cyclic phosphodiesterase (PDE5A)
ATGGAGCGGGCCGGCCCCAGCTTCGGGCAGCAGCGACAGCAGCAGCAGCCCCAGCAGCAG
AAGCAGCAGCAGAGGGATCAGGACTCGGTCGAAGCATGGCTGGACGATCACTGGGACTTT
ACCTTCTCATACTTTGTTAGAAAAGCCACCAGAGAAATGGTCAATGCATGGTTTGCTGAG
AGAGTTCACACCATCCCTGTGTGCAAGGAAGGTATCAGAGGCCACACCGAATCTTGCTCT
TGTCCCTTGCAGCAGAGTCCTCGTGCAGATAACAGTGCCCCTGGAACACCAACCAGGAAA
ATCTCTGCCTCTGAATTTGACCGGCCTCTTAGACCCATTGTTGTCAAGGATTCTGAGGGA
ACTGTGAGCTTCCTCTCTGACTCAGAAAAGAAGGAACAGATGCCTCTAACCCCTCCAAGG
TTTGATCATGATGAAGGGGACCAGTGCTCAAGACTCTTGGAATTAGTGAAGGATATTTCT
AGTCATTTGGATGTCACAGCCTTATGTCACAAAATTTTCTTGCATATCCATGGACTGATA
TCTGCTGACCGCTATTCCCTGTTCCTTGTCTGTGAAGACAGCTCCAATGACAAGTTTCTT
ATCAGCCGCCTCTTTGATGTTGCTGAAGGTTCAACACTGGAAGAAGTTTCAAATAACTGT
ATCCGCTTAGAATGGAACAAAGGCATTGTGGGACATGTGGCAGCGCTTGGTGAGCCCTTG
AACATCAAAGATGCATATGAGGATCCTCGGTTCAATGCAGAAGTTGACCAAATTACAGGC
TACAAGACACAAAGCATTCTTTGTATGCCAATTAAGAATCATAGGGAAGAGGTTGTTGGT
GTAGCCCAGGCCATCAACAAGAAATCAGGAAACGGTGGGACATTTACTGAAAAAGATGAA
AAGGACTTTGCTGCTTATTTGGCATTTTGTGGTATTGTTCTTCATAATGCTCAGCTCTAT
GAGACTTCACTGCTGGAGAACAAGAGAAATCAGGTGCTGCTTGACCTTGCTAGTTTAATT
TTTGAAGAACAACAATCATTAGAAGTAATTTTGAAGAAAATAGCTGCCACTATTATCTCT
TTCATGCAAGTGCAGAAATGCACCATTTTCATAGTGGATGAAGATTGCTCCGATTCTTTT
TCTAGTGTGTTTCACATGGAGTGTGAGGAATTAGAAAAATCATCTGATACATTAACAAGG
GAACATGATGCAAACAAAATCAATTACATGTATGCTCAGTATGTCAAAAATACTATGGAA
CCACTTAATATCCCAGATGTCAGTAAGGATAAAAGATTTCCCTGGACAACTGAAAATACA
GGAAATGTAAACCAGCAGTGCATTAGAAGTTTGCTTTGTACACCTATAAAAAATGGAAAG
AAGAATAAAGTTATAGGGGTTTGCCAACTTGTTAATAAGATGGAGGAGAATACTGGCAAG
GTTAAGCCTTTCAACCGAAATGACGAACAGTTTCTGGAAGCTTTTGTCATCTTTTGTGGC
TTGGGGATCCAGAACACGCAGATGTATGAAGCAGTGGAGAGAGCCATGGCCAAGCAAATG
GTCACATTGGAGGTTCTGTCGTATCATGCTTCAGCAGCAGAGGAAGAAACAAGAGAGCTA
CAGTCGTTAGCGGCTGCTGTGGTGCCATCTGCCCAGACCCTTAAAATTACTGACTTTAGC
TTCAGTGACTTTGAGCTGTCTGATCTGGAAACAGCACTGTGTACAATTCGGATGTTTACT
GACCTCAACCTTGTGCAGAACTTCCAGATGAAACATGAGGTTCTTTGCAGATGGATTTTA
AGTGTTAAGAAGAATTATCGGAAGAATGTTGCCTATCATAATTGGAGACATGCCTTTAAT
ACAGCTCAGTGCATGTTTGCTGCTCTAAAAGCAGGCAAAATTCAGAACAAGCTGACTGAC
CTGGAGATACTTGCATTGCTGATTGCTGCACTAAGCCACGATTTGGATCACCGTGGTGTG
AATAACTCTTACATACAGCGAAGTGAACATCCACTTGCCCAGCTTTACTGCCATTCAATC
ATGGAACACCATCATTTTGACCAGTGCCTGATGATTCTTAATAGTCCAGGCAATCAGATT
CTCAGTGGCCTCTCCATTGAAGAATATAAGACCACGTTGAAAATAATCAAGCAAGCTATT
TTAGCTACAGACCTAGCACTGTACATTAAGAGGCGAGGAGAATTTTTTGAACTTATAAGA
AAAAATCAATTCAATTTGGAAGATCCTCATCAAAAGGAGTTGTTTTTGGCAATGCTGATG
ACAGCTTGTGATCTTTCTGCAATTACAAAACCCTGGCCTATTCAACAACGGATAGCAGAA
CTTGTAGCAACTGAATTTTTTGATCAAGGAGACAGAGAGAGAAAAGAACTCAACATAGAA
CCCACTGATCTAATGAACAGGGAGAAGAAAAACAAAATCCCAAGTATGCAAGTTGGGTTC
ATAGATGCCATCTGCTTGCAACTGTATGAGGCCCTGACCCACGTGTCAGAGGACTGTTTC
CCTTTGCTAGATGGCTGCAGAAAGAACAGGCAGAAATGGCAGGCCCTTGCAGAACAGCAG
GAGAAGATGCTGATTAATGGGGAAAGCGGCCAGGCCAAGCGGAACTGA
Chromosome Location
4
Locus
4q25-q27
External Identifiers
ResourceLink
UniProtKB IDO76074
UniProtKB Entry NamePDE5A_HUMAN
GenBank Protein ID3420185
GenBank Gene IDAF043731
GenAtlas IDPDE5A
HGNC IDHGNC:8784
General References
  1. Loughney K, Hill TR, Florio VA, Uher L, Rosman GJ, Wolda SL, Jones BA, Howard ML, McAllister-Lucas LM, Sonnenburg WK, Francis SH, Corbin JD, Beavo JA, Ferguson K: Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase. Gene. 1998 Aug 17;216(1):139-47. [PubMed:9714779]
  2. Yanaka N, Kotera J, Ohtsuka A, Akatsuka H, Imai Y, Michibata H, Fujishige K, Kawai E, Takebayashi S, Okumura K, Omori K: Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. Eur J Biochem. 1998 Jul 15;255(2):391-9. [PubMed:9716380]
  3. Stacey P, Rulten S, Dapling A, Phillips SC: Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5). Biochem Biophys Res Commun. 1998 Jun 18;247(2):249-54. [PubMed:9642111]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621]
  6. 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]
  7. Zhou L, Thompson WJ, Potter DE: Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1999 Jul;40(8):1745-52. [PubMed:10393044]
  8. Rybalkin SD, Rybalkina IG, Feil R, Hofmann F, Beavo JA: Regulation of cGMP-specific phosphodiesterase (PDE5) phosphorylation in smooth muscle cells. J Biol Chem. 2002 Feb 1;277(5):3310-7. Epub 2001 Nov 26. [PubMed:11723116]
  9. Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, Moon J, Yoon JM, Hyun YL, Kim E, Eum SJ, Park SY, Lee JO, Lee TG, Ro S, Cho JM: Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature. 2003 Sep 4;425(6953):98-102. [PubMed:12955149]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00203Sildenafilapproved, investigationalyesinhibitorDetails
DB00862VardenafilapprovedyesinhibitorDetails
DB00975DipyridamoleapprovedyesinhibitorDetails
DB01972Guanosine-5'-MonophosphateexperimentalunknownDetails
DB03597gamma-Glutamyl[S-(2-iodobenzyl)cysteinyl]glycineexperimentalunknownDetails
DB04272Citric acidapproved, nutraceutical, vet_approvedunknownDetails
DB00806Pentoxifyllineapproved, investigationalyesinhibitorDetails
DB00277TheophyllineapprovedyesinhibitorDetails
DB00820Tadalafilapproved, investigationalyesinhibitorDetails
DB05415OSI-461investigationalunknownDetails
DB06237AvanafilapprovedyesinhibitorDetails
DB06246ExisulindinvestigationalunknownDetails
DB06267Udenafilapproved, investigationalyesinhibitorDetails
DB079543-isobutyl-1-methyl-7H-xanthineexperimentalunknownDetails
DB087295-ethoxy-4-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)thiophene-2-sulfonamideexperimentalunknownDetails
DB09282Molsidomineapproved, investigationalunknownsubstrateDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB09283TrapidilexperimentalyesinhibitorDetails
DB00201CaffeineapprovedyesinhibitorDetails