cGMP-dependent 3',5'-cyclic phosphodiesterase

Details

Name
cGMP-dependent 3',5'-cyclic phosphodiesterase
Synonyms
  • 3.1.4.17
  • CGS-PDE
  • cGSPDE
  • Cyclic GMP-stimulated phosphodiesterase
Gene Name
PDE2A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004088|cGMP-dependent 3',5'-cyclic phosphodiesterase
MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPPPQPCADSLQDALLSLGSVIDI
SGLQRAVKEALSAVLPRVETVYTYLLDGESQLVCEDPPHELPQEGKVREAIISQKRLGCN
GLGFSDLPGKPLARLVAPLAPDTQVLVMPLADKEAGAVAAVILVHCGQLSDNEEWSLQAV
EKHTLVALRRVQVLQQRGPREAPRAVQNPPEGTAEDQKGGAAYTDRDRKILQLCGELYDL
DASSLQLKVLQYLQQETRASRCCLLLVSEDNLQLSCKVIGDKVLGEEVSFPLTGCLGQVV
EDKKSIQLKDLTSEDVQQLQSMLGCELQAMLCVPVISRATDQVVALACAFNKLEGDLFTD
EDEHVIQHCFHYTSTVLTSTLAFQKEQKLKCECQALLQVAKNLFTHLDDVSVLLQEIITE
ARNLSNAEICSVFLLDQNELVAKVFDGGVVDDESYEIRIPADQGIAGHVATTGQILNIPD
AYAHPLFYRGVDDSTGFRTRNILCFPIKNENQEVIGVAELVNKINGPWFSKFDEDLATAF
SIYCGISIAHSLLYKKVNEAQYRSHLANEMMMYHMKVSDDEYTKLLHDGIQPVAAIDSNF
ASFTYTPRSLPEDDTSMAILSMLQDMNFINNYKIDCPTLARFCLMVKKGYRDPPYHNWMH
AFSVSHFCYLLYKNLELTNYLEDIEIFALFISCMCHDLDHRGTNNSFQVASKSVLAALYS
SEGSVMERHHFAQAIAILNTHGCNIFDHFSRKDYQRMLDLMRDIILATDLAHHLRIFKDL
QKMAEVGYDRNNKQHHRLLLCLLMTSCDLSDQTKGWKTTRKIAELIYKEFFSQGDLEKAM
GNRPMEMMDREKAYIPELQISFMEHIAMPIYKLLQDLFPKAAELYERVASNREHWTKVSH
KFTIRGLPSNNSLDFLDEEYEVPDLDGTRAPINGCCSLDAE
Number of residues
941
Molecular Weight
105715.85
Theoretical pI
5.08
GO Classification
Functions
calcium channel activity / cAMP binding / cGMP binding / cGMP-stimulated cyclic-nucleotide phosphodiesterase activity / cyclic-nucleotide phosphodiesterase activity / drug binding / metal ion binding / protein homodimerization activity / TPR domain binding
Processes
blood coagulation / calcium ion transmembrane transport / cAMP catabolic process / cAMP-mediated signaling / cellular response to cGMP / cellular response to drug / cellular response to granulocyte macrophage colony-stimulating factor stimulus / cellular response to macrophage colony-stimulating factor stimulus / cellular response to mechanical stimulus / cellular response to transforming growth factor beta stimulus / cGMP catabolic process / cGMP-mediated signaling / establishment of endothelial barrier / metabolic process / monocyte differentiation / negative regulation of cAMP biosynthetic process / negative regulation of protein import into nucleus, translocation / negative regulation of transcription from RNA polymerase II promoter / negative regulation of vascular permeability / positive regulation of inflammatory response / positive regulation of vascular permeability / protein targeting to mitochondrion
Components
cytoplasm / cytosol / endoplasmic reticulum / Golgi apparatus / membrane raft / mitochondrial matrix / nucleus / perinuclear region of cytoplasm / plasma membrane / presynaptic membrane
General Function
Tpr domain binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.Isoform PDE2A2: Regulates Mitochondrial cAMP Levels and Respiration.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021934|cGMP-dependent 3',5'-cyclic phosphodiesterase (PDE2A)
ATGGTCCTGGTGCTGCACCACATCCTCATCGCTGTTGTCCAATTCCTCAGGCGGGGCCAG
CAGGTCTTCCTCAAGCCGGACGAGCCGCCGCCGCCGCCGCAGCCATGCGCCGACAGCCTG
CAGGACGCCTTGCTGAGTCTGGGCTCTGTCATCGACATTTCAGGCCTGCAACGTGCTGTC
AAGGAGGCCCTGTCAGCTGTGCTCCCCCGAGTGGAAACTGTCTACACCTACCTACTGGAT
GGTGAGTCCCAGCTGGTGTGTGAGGACCCCCCACATGAGCTGCCCCAGGAGGGGAAAGTC
CGGGAGGCTATCATCTCCCAGAAGCGGCTGGGCTGCAATGGGCTGGGCTTCTCAGACCTG
CCAGGGAAGCCCTTGGCCAGGCTGGTGGCTCCACTGGCTCCTGATACCCAAGTGCTGGTC
ATGCCGCTAGCGGACAAGGAGGCTGGGGCCGTGGCAGCTGTCATCTTGGTGCACTGTGGC
CAGCTGAGTGATAATGAGGAATGGAGCCTGCAGGCGGTGGAGAAGCATACCCTGGTCGCC
CTGCGGAGGGTGCAGGTCCTGCAGCAGCGCGGGCCCAGGGAGGCTCCCCGAGCCGTCCAG
AACCCCCCGGAGGGGACGGCGGAAGACCAGAAGGGCGGGGCGGCGTACACCGACCGCGAC
CGCAAGATCCTCCAACTGTGCGGGGAACTCTACGACCTGGATGCCTCTTCCCTGCAGCTC
AAAGTGCTCCAATACCTGCAGCAGGAGACCCGGGCATCCCGCTGCTGCCTCCTGCTGGTG
TCGGAGGACAATCTCCAGCTTTCTTGCAAGGTCATCGGAGACAAAGTGCTCGGGGAAGAG
GTCAGCTTTCCCTTGACAGGATGCCTGGGCCAGGTGGTGGAAGACAAGAAGTCCATCCAG
CTGAAGGACCTCACCTCCGAGGATGTACAACAGCTGCAGAGCATGTTGGGCTGTGAGCTG
CAGGCCATGCTCTGTGTCCCTGTCATCAGCCGGGCCACTGACCAGGTGGTGGCCTTGGCC
TGCGCCTTCAACAAGCTAGAAGGAGACTTGTTCACCGACGAGGACGAGCATGTGATCCAG
CACTGCTTCCACTACACCAGCACCGTGCTCACCAGCACCCTGGCCTTCCAGAAGGAACAG
AAACTCAAGTGTGAGTGCCAGGCTCTTCTCCAAGTGGCAAAGAACCTCTTCACCCACCTG
GATGACGTCTCTGTCCTGCTCCAGGAGATCATCACGGAGGCCAGAAACCTCAGCAACGCA
GAGATCTGCTCTGTGTTCCTGCTGGATCAGAATGAGCTGGTGGCCAAGGTGTTCGACGGG
GGCGTGGTGGATGATGAGAGCTATGAGATCCGCATCCCGGCCGATCAGGGCATCGCGGGA
CACGTGGCGACCACGGGCCAGATCCTGAACATCCCTGACGCATATGCCCATCCGCTTTTC
TACCGCGGCGTGGACGACAGCACCGGCTTCCGCACGCGCAACATCCTCTGCTTCCCCATC
AAGAACGAGAACCAGGAGGTCATCGGTGTGGCCGAGCTGGTGAACAAGATCAATGGGCCA
TGGTTCAGCAAGTTCGACGAGGACCTGGCGACGGCCTTCTCCATCTACTGCGGCATCAGC
ATCGCCCATTCTCTCCTATACAAAAAAGTGAATGAGGCTCAGTATCGCAGCCACCTGGCC
AATGAGATGATGATGTACCACATGAAGGTCTCCGATGATGAGTATACCAAACTTCTCCAT
GATGGGATCCAGCCTGTGGCTGCCATTGACTCCAATTTTGCAAGTTTCACCTATACCCCT
CGTTCCCTGCCCGAGGATGACACGTCCATGGCCATCCTGAGCATGCTGCAGGACATGAAT
TTCATCAACAACTACAAAATTGACTGCCCGACCCTGGCCCGGTTCTGTTTGATGGTGAAG
AAGGGCTACCGGGATCCCCCCTACCACAACTGGATGCACGCCTTTTCTGTCTCCCACTTC
TGCTACCTGCTCTACAAGAACCTGGAGCTCACCAACTACCTCGAGGACATCGAGATCTTT
GCCTTGTTTATTTCCTGCATGTGTCATGACCTGGACCACAGAGGCACAAACAACTCTTTC
CAGGTGGCCTCGAAATCTGTGCTGGCTGCGCTCTACAGCTCTGAGGGCTCCGTCATGGAG
AGGCACCACTTTGCTCAGGCCATCGCCATCCTCAACACCCACGGCTGCAACATCTTTGAT
CATTTCTCCCGGAAGGACTATCAGCGCATGCTGGATCTGATGCGGGACATCATCTTGGCC
ACAGACCTGGCCCACCATCTCCGCATCTTCAAGGACCTCCAGAAGATGGCTGAGGTGGGC
TACGACCGAAACAACAAGCAGCACCACAGACTTCTCCTCTGCCTCCTCATGACCTCCTGT
GACCTCTCTGACCAGACCAAGGGCTGGAAGACTACGAGAAAGATCGCGGAGCTGATCTAC
AAAGAATTCTTCTCCCAGGGAGACCTGGAGAAGGCCATGGGCAACAGGCCGATGGAGATG
ATGGACCGGGAGAAGGCCTATATCCCTGAGCTGCAAATCAGCTTCATGGAGCACATTGCA
ATGCCCATCTACAAGCTGTTGCAGGACCTGTTCCCCAAAGCGGCAGAGCTGTACGAGCGC
GTGGCCTCCAACCGTGAGCACTGGACCAAGGTGTCCCACAAGTTCACCATCCGCGGCCTC
CCAAGTAACAACTCGCTGGACTTCCTGGATGAGGAGTACGAGGTGCCTGATCTGGATGGC
ACTAGGGCCCCCATCAATGGCTGCTGCAGCCTTGATGCTGAGTGA
Chromosome Location
11
Locus
11q13.4
External Identifiers
ResourceLink
UniProtKB IDO00408
UniProtKB Entry NamePDE2A_HUMAN
GenBank Protein ID2108052
GenBank Gene IDU67733
GenAtlas IDPDE2A
HGNC IDHGNC:8777
General References
  1. Rosman GJ, Martins TJ, Sonnenburg WK, Beavo JA, Ferguson K, Loughney K: Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3',5'-cyclic nucleotide phosphodiesterase. Gene. 1997 May 20;191(1):89-95. [PubMed:9210593]
  2. 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]
  3. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811]
  4. Russwurm C, Zoidl G, Koesling D, Russwurm M: Dual acylation of PDE2A splice variant 3: targeting to synaptic membranes. J Biol Chem. 2009 Sep 18;284(38):25782-90. doi: 10.1074/jbc.M109.017194. Epub 2009 Jul 24. [PubMed:19632989]
  5. 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]
  6. Suzuki T, Moriya K, Nagatoshi K, Ota Y, Ezure T, Ando E, Tsunasawa S, Utsumi T: Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system. Proteomics. 2010 May;10(9):1780-93. doi: 10.1002/pmic.200900783. [PubMed:20213681]
  7. Acin-Perez R, Russwurm M, Gunnewig K, Gertz M, Zoidl G, Ramos L, Buck J, Levin LR, Rassow J, Manfredi G, Steegborn C: A phosphodiesterase 2A isoform localized to mitochondria regulates respiration. J Biol Chem. 2011 Sep 2;286(35):30423-32. doi: 10.1074/jbc.M111.266379. Epub 2011 Jul 1. [PubMed:21724846]
  8. Iffland A, Kohls D, Low S, Luan J, Zhang Y, Kothe M, Cao Q, Kamath AV, Ding YH, Ellenberger T: Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system. Biochemistry. 2005 Jun 14;44(23):8312-25. [PubMed:15938621]
  9. Pandit J, Forman MD, Fennell KF, Dillman KS, Menniti FS: Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct. Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18225-30. doi: 10.1073/pnas.0907635106. Epub 2009 Oct 14. [PubMed:19828435]
  10. Zhu J, Yang Q, Dai D, Huang Q: X-ray crystal structure of phosphodiesterase 2 in complex with a highly selective, nanomolar inhibitor reveals a binding-induced pocket important for selectivity. J Am Chem Soc. 2013 Aug 14;135(32):11708-11. doi: 10.1021/ja404449g. Epub 2013 Aug 2. [PubMed:23899287]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02315Cyclic GMPexperimentalunknownDetails
DB05142ND7001investigationalunknownDetails
DB06246ExisulindinvestigationalunknownDetails
DB079543-isobutyl-1-methyl-7H-xanthineexperimentalunknownDetails
DB08811TofisopamexperimentalunknowninhibitorDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB09283TrapidilexperimentalyesinhibitorDetails