Skip to main content
SpringerLink
Log in

ADCY9 (Adenylyl Cyclase 9)

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 235 Accesses

Synonyms

AC9; ACIX; Adcy9; ADCY9; Adenylate cyclase 9; Adenylyl cyclase type 9

Historical Background

Adenylyl cyclase (AC) is the enzyme (EC 4.6.1.1) that converts Mg-ATP to adenosine 3′:5′ monophosphate or cyclic AMP and pyrophosphate first reported in 1958 by Sutherland and Rall. Eventually, a membrane-delimited biochemical cascade (Fig. 1) was discovered as the molecular machinery of signal transduction by cell surface receptors via heterotrimeric G proteins (Antoni 2000). The era of gene cloning revealed an unexpectedly complex structure of membrane-bound adenylyl cyclase: a single large polypeptide chain that crosses the plasma membrane 12 times, the catalytic core being formed between two structurally homologous cytoplasmic domains (C1a and C2a) held together by noncovalent interactions (Fig. 2). The crystal structures of these domains in complex with Gsα and the likely mechanisms underlying catalysis have been reported (Tesmer and Sprang 1998). There are nine genes encoding...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Alper S, Laws R, Lackford B, Boyd WA, Dunlap P, Freedman JH, Schwartz DA. Identification of innate immunity genes and pathways using a comparative genomics approach. Proc Natl Acad Sci U S A. 2008;105(19):7016–21. doi:0.1073/pnas.0802405105.

    Google Scholar 

  • Antoni FA, Wiegand U, Black J, Simpson J. Cellular localisation of adenylyl cyclase: a post-genome perspective. Neurochem Res. 2006;31(2):287–95.

    Article  CAS  PubMed  Google Scholar 

  • Antoni FA. Molecular diversity of cyclic AMP signaling. Front Neuroendocrinol. 2000;21:103–32.

    Article  CAS  PubMed  Google Scholar 

  • Antoni FA. New paradigms in cAMP signalling. Mol Cell Endocrinol. 2012;353(1–2):3–9. doi:10.1016/j.mce.2011.10.034.

    Article  CAS  PubMed  Google Scholar 

  • Antoni FA, Barnard RJO, Shipston MJ, Smith SM, Simpson J, Paterson JM. Calcineurin feedback inhibition of agonist-evoked cAMP formation. J Biol Chem. 1995;270:28055–61.

    Article  CAS  PubMed  Google Scholar 

  • Antoni FA, Palkovits M, Simpson J, Smith SM, Leitch AL, Rosie R, Fink G, Paterson JM. Ca2+/calcineurin-inhibited adenylyl cyclase highly abundant in forebrain regions important for learning and memory. J Neurosci. 1998a;18(23):9650–61.

    CAS  PubMed  Google Scholar 

  • Antoni FA, Smith SM, Simpson J, Rosie R, Fink G, Paterson JM. Calcium control of adenylyl cyclase – the calcineurin connection. Adv Second Messenger Phosphoprotein Res. 1998b;32:153–72.

    Article  CAS  PubMed  Google Scholar 

  • Brand CS, Hocker HJ, Gorfe AA, Cavasotto CN, Dessauer CW. Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds. J Pharmacol Exp Ther. 2013;347(2):265–75. doi:10.1124/jpet.113.208157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cumbay MG, Watts VJ. Novel regulatory properties of human type 9 adenylate cyclase. J Pharmacol Exp Ther. 2004;310(1):108–15. doi:10.1124/jpet.104.065748.

    Article  CAS  PubMed  Google Scholar 

  • Dvir M, Strulovich R, Sachyani D, Cohen IB-T, Haitin Y, Dessauer C, Pongs O, Kass R, Hirsch JA, Attali B. Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I-KS regulation by PKA and PIP2. J Cell Sci. 2014;127(18):3943–55. doi:10.1242/jcs.147033.

    Article  CAS  PubMed  Google Scholar 

  • Hacker BM, Tomlinson JE, Wayman GA, Sultana R, Chan G, Villacres E, Disteche C, Storm DR. Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9). Genomics. 1998;50(1):97–104. doi:10.1006/geno.1998.5293.

    Article  CAS  PubMed  Google Scholar 

  • Halls ML, Cooper DMF. Regulation by Ca(2+)-signaling pathways of adenylyl cyclases. Cold Spring Harb Perspect Biol. 2011;3(1). doi:10.1101/cshperspect.a004143.

    Google Scholar 

  • Haunsø A, Simpson J, Antoni FA. Small ligands modulating the activity of mammalian adenylyl cyclases: A novel mode of inhibition by calmidazolium. Mol Pharmacol. 2003;63:624–31.

    Article  PubMed  Google Scholar 

  • Houslay MD. Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem Science. 2010;35(2):91–100. doi:10.1016/j.tibs.2009.09.007.

    Article  CAS  Google Scholar 

  • Johannessen CM, Johnson LA, Piccioni F, Townes A, Frederick DT, Donahue MK, Narayan R, Flaherty KT, Wargo JA, Root DE, Garraway LA. A melanocyte lineage program confers resistance to MAP kinase pathway inhibition. Nature. 2013;504(7478):138–42. doi:10.1038/nature12688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lefkimmiatis K, Zaccolo M. cAMP signaling in subcellular compartments. Pharmacol Ther. 2014;143(3):295–304. doi:10.1016/j.pharmthera.2014.03.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Chen L, Kass RS, Dessauer CW. The A-kinase anchoring protein Yotiao facilitates complex formation between adenylyl cyclase type 9 and the IKs potassium channel in heart. J Biol Chem. 2012;287(35):29815–24. doi:10.1074/jbc.M112.380568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mons N, Segu L, Nogues X, Buhot M. Effects of age and spatial learning on adenylyl cyclase mRNA expression in the mouse hippocampus. Neurobiol Aging. 2004;25(8):1095–106.

    Article  CAS  PubMed  Google Scholar 

  • Niesor EJ, Benghozi R, Amouyel P, Ferdinand KC, Schwartz GG. Adenylyl cyclase 9 polymorphisms reveal potential link to HDL function and cardiovascular events in multiple pathologies: Potential implications in sickle cell disease. Cardiovasc Drugs Ther. 2015;29(6):563–72. doi:10.1007/s10557-015-6626-1.

    Article  CAS  PubMed  Google Scholar 

  • Osteen JD, Sampson KJ, Kass RS. The cardiac IKs channel, complex indeed. Proc Natl Acad Sci U S A. 2010;107(44):18751–2. doi:10.1073/pnas.1014150107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paterson JM, Smith SM, Simpson J, Grace OC, Sosunov AA, Bell J, Antoni FA. Characterisation of human adenylyl cyclase IX reveals inhibition by Ca2+/calcineurin and differential mRNA polyadenylation. J Neurochem. 2000;75(4):1358–67.

    Article  CAS  PubMed  Google Scholar 

  • Piggott LA, Bauman AL, Scott JD, Dessauer CW. The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain. Proc Natl Acad Sci U S A. 2008;105(37):13835–40. doi:10.1073/pnas.0712100105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Premont RT, Matsuoka I, Mattei M-G, Pouille Y, Defer N, Hanoune J. Identification and characterization of a widely expressed from of adenylyl cyclase. J Biol Chem. 1996;271:13900–7.

    Article  CAS  PubMed  Google Scholar 

  • Simpson J, Morrice N, Chen P, Antoni FA. Regulation of adenylyl cyclase 9 by cyclin-dependent protein kinase 5 (cdk5). Bioscience 2006. Glasgow: Portland Press; 2006. 0449.

    Google Scholar 

  • Small K, Brown K, Theiss C, Seman C, Weiss S, Liggett S. An Ile to Met polymorphism in the catalytic domain of adenylyl cyclase type 9 confers reduced beta2-adrenergic receptor stimulation. Pharmacogenetics. 2003;13(9):535–41.

    Article  CAS  PubMed  Google Scholar 

  • Tardif JC, Rheaume E, Lemieux Perreault LP, Gregoire JC, Feroz Zada Y, Asselin G, Provost S, Barhdadi A, Rhainds D, L'Allier PL, Ibrahim R, Upmanyu R, Niesor EJ, Benghozi R, Suchankova G, Laghrissi-Thode F, Guertin MC, Olsson AG, Mongrain I, Schwartz GG, Dube MP. Pharmacogenomic determinants of the cardiovascular effects of dalcetrapib. Circ Cardiovasc Genet. 2015;8(2):372–82. doi:10.1161/circgenetics.114.000663.

    Article  CAS  PubMed  Google Scholar 

  • Tesmer J, Sprang S. The structure, catalytic mechanism and regulation of adenylyl cyclase. Curr Opin Struct Biol. 1998;8(6):713–9.

    Article  CAS  PubMed  Google Scholar 

  • Toyota T, Yamada K, Saito K, Detera-Wadleigh S, Yoshikawa T. Association analysis of adenylate cyclase type 9 gene using pedigree disequilibrium test in bipolar disorder. Mol Psychiatry. 2002;7(5):450–2.

    Article  CAS  PubMed  Google Scholar 

  • Yan SZ, Huang ZH, Andrews RK, Tang WJ. Conversion of forskolin-insensitive to forskolin-sensitive (mouse-type IX) adenylyl cyclase. Mol Pharmacol. 1998;53(2):182–7.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Integrative Physiology, University of Edinburgh, Edinburgh, Scotland, UK

    Ferenc AndrĂ¡s Antoni

Authors
  1. Ferenc AndrĂ¡s Antoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ferenc AndrĂ¡s Antoni .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Antoni, F.A. (2016). ADCY9 (Adenylyl Cyclase 9). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_140-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_140-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation