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Gene Review

ADCY3  -  adenylate cyclase 3

Homo sapiens

Synonyms: AC-III, AC3, ATP pyrophosphate-lyase 3, Adenylate cyclase type 3, Adenylate cyclase type III, ...
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Disease relevance of ADCY3

  • Measured global EF values in 14 patients without coronary stenosis were 52.3% +/- 7.6% (AC1), 60.6% +/- 8.9% (AC2) and 55.6% +/- 5.6% (AC3), and those in 11 patients with severe ischaemia were 53.6% +/- 8.0% (AC1), 45.6% +/- 12.1% (AC2) and 49.7% +/- 10.7% [1].

High impact information on ADCY3

  • This review will discuss the role of adenylate cyclases as coincidence detectors in the nervous system with special focus on adenylate cyclase type III, an isoenzyme that is found in large quantities in olfactory receptor neurons [2].
  • Electrophoresis of aldolase from adult retina revealed the presence of all potential A-C hybrids (A4, A3C, A2C2, AC3, and C4) [3].
  • We conclude that persistent inhibition of AC (probably AC-3) by vasopressin is mediated by inositol trisphosphate-evoked Ca2+ release causing activation of Ca2+-calmodulin-dependent protein kinase II [4].
  • The co-expression of wild type or N54-alpha(s) along with the thyroid-stimulating hormone (TSH) receptor and adenylyl cyclase isotypes differing with respect to betagamma stimulation (AC II or AC III) revealed that the phenotype of the mutant is not dependent upon the presence of adenylyl cyclase isoforms regulated by betagamma [5].
  • Adenylyl cyclase 3 mediates prostaglandin E(2)-induced growth inhibition in arterial smooth muscle cells [6].

Biological context of ADCY3

  • Comparison of the translated amino acid sequence of the AC3 gene between human and rat shows 95% homology [7].
  • Here we report cloning of a full-length cDNA encoding human AC3 from a human fetal brain cDNA library using a PCR-based screening method [7].
  • This wide distribution of AC3 expression may involve a number of physiological and pathophysiological metabolic processes [7].
  • We recently demonstrated the presence in GK rats of two functional point mutations in the promoter region of the type 3 adenylyl cyclase (AC3) gene that resulted in overexpression of AC3 mRNA associated with increased cAMP generation [7].
  • Coupling of odorant receptors to AC3 stimulates cAMP transients that function as the major second messenger for olfactory signaling [8].

Anatomical context of ADCY3

  • Inhibitory adenylyl cyclase 3 antibodies interfered with ACTH action only in the zona fasciculata [9].
  • Using RT-PCR, clear AC3 expression was detected in isolated human islets as well as a cDNA panel containing templates from eight different tissues (brain, heart, kidney, liver, lung, pancreas, placenta, and skeletal muscle) [7].
  • RT-PCR screening of platelet, buffy coat layer cell and bone marrow megakaryocyte cDNA, and Western blot analysis with AC type III (AC-III) antibodies identified AC-III in platelets and in megakaryocytes [10].
  • Thus, the presence in myometrium of AC II family (types II, IV, VII) confers ability to G inhibitory proteins to stimulate enzyme activity via betagamma complexes at mid-pregnancy, whereas expression of AC III, V, and VI isoforms confers to the myometrial AC system a high sensitivity to inhibition by Ca2+-dependent processes at term [11].
  • In the present study, ACI, ACIII, and ACVIII were heterologously expressed in HEK 293 cells, and conditions were devised that distinguished capacitative Ca2+ entry from both internal release and nonspecific elevation in [Ca2+]i around the plasma membrane [12].

Associations of ADCY3 with chemical compounds

  • Both platelet AC and cloned AC-III required Mg(2+) for activity, were insensitive to Ca(2+) and were G(s)- and G(i)-coupled [10].
  • Unlike the AC-II and AC-III active sites that utilize two-Asp motifs for cation binding, the AC-IV active site is relatively enriched in glutamate and features an ExE motif as its most conserved element [13].
  • In addition to AC-3, a distinct cysteine protease cDNA, AC-4, was amplified by the same oligonucleotide primers. cDNAs encoding a fifth cysteine protease, AC-5, were isolated from an adult worm cDNA expression library using specific rabbit antisera and by PCR [14].
  • These chimeric mutants were derived from 3 isoforms of AC: AC7 (type 7), the most ethanol responsive isoform; AC3 (type 3), an isoform that is far less responsive to ethanol; and AC2 (type 2), an isoform that is homologous to AC7 but less responsive to ethanol [15].

Regulatory relationships of ADCY3


Analytical, diagnostic and therapeutic context of ADCY3

  • A cDNA that appears to be a near full-length copy of the AC-3 gene was isolated using the polymerase chain reaction (PCR) technique to amplify cDNAs from adult worm poly(A)+ mRNAs [14].


  1. Gated single-photon emission tomography imaging protocol to evaluate myocardial stunning after exercise. Hashimoto, J., Kubo, A., Iwasaki, R., Iwanaga, S., Mitamura, H., Ogawa, S., Kosuda, S. European journal of nuclear medicine. (1999) [Pubmed]
  2. Signal integration in the nervous system: adenylate cyclases as molecular coincidence detectors. Anholt, R.R. Trends Neurosci. (1994) [Pubmed]
  3. Characterization of some glycolytic enzymes from human retina and retinoblastoma. Beemer, F.A., Vlug, A.M., Rijksen, G., Hamburg, A., Staal, G.E. Cancer Res. (1982) [Pubmed]
  4. Long lasting inhibition of adenylyl cyclase selectively mediated by inositol 1,4,5-trisphosphate-evoked calcium release. Dyer, J.L., Liu, Y., de la Huerga, I.P., Taylor, C.W. J. Biol. Chem. (2005) [Pubmed]
  5. A dominant negative Galphas mutant that prevents thyroid-stimulating hormone receptor activation of cAMP production and inositol 1,4,5-trisphosphate turnover: competition by different G proteins for activation by a common receptor. Cleator, J.H., Ravenell, R., Kurtz, D.T., Hildebrandt, J.D. J. Biol. Chem. (2004) [Pubmed]
  6. Adenylyl cyclase 3 mediates prostaglandin E(2)-induced growth inhibition in arterial smooth muscle cells. Wong, S.T., Baker, L.P., Trinh, K., Hetman, M., Suzuki, L.A., Storm, D.R., Bornfeldt, K.E. J. Biol. Chem. (2001) [Pubmed]
  7. Molecular cloning of a full-length cDNA for human type 3 adenylyl cyclase and its expression in human islets. Yang, B., He, B., Abdel-Halim, S.M., Tibell, A., Brendel, M.D., Bretzel, R.G., Efendic, S., Hillert, J. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  8. Calmodulin-regulated adenylyl cyclases: cross-talk and plasticity in the central nervous system. Wang, H., Storm, D.R. Mol. Pharmacol. (2003) [Pubmed]
  9. Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland. Côté, M., Guillon, G., Payet, M.D., Gallo-Payet, N. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  10. Molecular and biochemical evidence for the presence of type III adenylyl cyclase in human platelets. Katsel, P.L., Tagliente, T.M., Schwarz, T.E., Craddock-Royal, B.D., Patel, N.D., Maayani, S. Platelets (2003) [Pubmed]
  11. Molecular diversity of adenylyl cyclases in human and rat myometrium. Correlation with global adenylyl cyclase activity during mid- and term pregnancy. Mhaouty-Kodja, S., Bouet-Alard, R., Limon-Boulez, I., Maltier, J.P., Legrand, C. J. Biol. Chem. (1997) [Pubmed]
  12. Functional co-localization of transfected Ca(2+)-stimulable adenylyl cyclases with capacitative Ca2+ entry sites. Fagan, K.A., Mahey, R., Cooper, D.M. J. Biol. Chem. (1996) [Pubmed]
  13. Structure of the Class IV Adenylyl Cyclase Reveals a Novel Fold. Gallagher, D.T., Smith, N.N., Kim, S.K., Heroux, A., Robinson, H., Reddy, P.T. J. Mol. Biol. (2006) [Pubmed]
  14. Cloning and sequence comparisons of four distinct cysteine proteases expressed by Haemonchus contortus adult worms. Pratt, D., Armes, L.G., Hageman, R., Reynolds, V., Boisvenue, R.J., Cox, G.N. Mol. Biochem. Parasitol. (1992) [Pubmed]
  15. Identification of ethanol responsive domains of adenylyl cyclase. Yoshimura, M., Pearson, S., Kadota, Y., Gonzalez, C.E. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  16. Components of the intracellular cAMP system supporting the olfactory reception of amyl alcohol. Bigdai, E.V., Samoilov, V.O. Neurosci. Behav. Physiol. (2003) [Pubmed]
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