Gene Symbol: Adcy6
Description: adenylate cyclase 6
Alias: AC6, mKIAA0422, adenylate cyclase type 6, ATP pyrophosphate-lyase 6, adenylate cyclase type VI, adenylyl cyclase 6, ca(2+)-inhibitable adenylyl cyclase
Species: mouse
Products:     Adcy6

Top Publications

  1. Gao M, Lai N, Giamouridis D, Kim Y, Guo T, Hammond H. Cardiac-directed expression of a catalytically inactive adenylyl cyclase 6 protects the heart from sustained β-adrenergic stimulation. PLoS ONE. 2017;12:e0181282 pubmed publisher
    Increased expression of adenylyl cyclase type 6 (AC6) has beneficial effects on the heart through cyclic adenosine monophosphate (cAMP)-dependent and cAMP-independent pathways...
  2. Grünberger C, Obermayer B, Klar J, Kurtz A, Schweda F. The calcium paradoxon of renin release: calcium suppresses renin exocytosis by inhibition of calcium-dependent adenylate cyclases AC5 and AC6. Circ Res. 2006;99:1197-206 pubmed
    ..its suppressive effects on renin secretion via the inhibition of the calcium-regulated adenylate cyclases AC5 and AC6. In primary cultures of JG cells, calcium-dependent inhibitors of renin release (angiotensin II, endothelin-1, ..
  3. Michalski N, Michel V, Bahloul A, Lefevre G, Barral J, Yagi H, et al. Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning. J Neurosci. 2007;27:6478-88 pubmed
    ..b>Adenylyl cyclase 6, which was found at the base of stereocilia, was both overexpressed and mislocated in Vlgr1-/- mice...
  4. Desch M, Schubert T, Schreiber A, Mayer S, Friedrich B, Artunc F, et al. PPARgamma-dependent regulation of adenylate cyclase 6 amplifies the stimulatory effect of cAMP on renin gene expression. Mol Endocrinol. 2010;24:2139-51 pubmed publisher
    ..mechanism involves potentiation of agonist-induced cAMP increase and up-regulation of adenylate cyclase 6 (AC6) gene expression. We identified a palindromic element with a 3-bp spacer (Pal3) in AC6 intron 1 (AC6Pal3)...
  5. Wu C, Lin J, Chien C, Chang W, Lai H, Chang C, et al. Type VI adenylyl cyclase regulates neurite extension by binding to Snapin and Snap25. Mol Cell Biol. 2011;31:4874-86 pubmed publisher
    ..We demonstrate here that type VI adenylyl cyclase (AC6), an enzyme which catalyzes cAMP synthesis, regulates neurite outgrowth by direct interaction with a binding ..
  6. von Hayn K, Werthmann R, Nikolaev V, Hommers L, Lohse M, Bünemann M. Gq-mediated Ca2+ signals inhibit adenylyl cyclases 5/6 in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2010;298:C324-32 pubmed publisher
    ..Furthermore, small interfering RNA (siRNA) knockdown of AC5 and AC6 (the two ACs known to be inhibited by Ca(2+)), significantly reduced the decrease of cAMP upon purinergic ..
  7. Fenton R, Murray F, Dominguez Rieg J, Tang T, Levi M, Rieg T. Renal phosphate wasting in the absence of adenylyl cyclase 6. J Am Soc Nephrol. 2014;25:2822-34 pubmed publisher
    ..We report here that mice lacking AC6 (AC6(-/-)) have increased plasma PTH and FGF-23 levels compared with wild-type (WT) mice but comparable plasma ..
  8. Birrell M, Bonvini S, Wortley M, Buckley J, Yew Booth L, Maher S, et al. The role of adenylyl cyclase isoform 6 in β-adrenoceptor signalling in murine airways. Br J Pharmacol. 2015;172:131-41 pubmed publisher
    ..Airway and vagal tissue expressed mRNA for various isoforms of AC. AC6 was the most prominent isoform...
  9. Tang T, Lai N, Wright A, Gao M, Lee P, Guo T, et al. Adenylyl cyclase 6 deletion increases mortality during sustained β-adrenergic receptor stimulation. J Mol Cell Cardiol. 2013;60:60-7 pubmed publisher
    ..Using a murine line with adenylyl cyclase 6 gene deletion (AC6KO), we tested the hypothesis that AC6 deletion, by limiting cAMP production, would ..

More Information


  1. Sugano Y, Lai N, Gao M, Firth A, Yuan J, Lew W, et al. Activated expression of cardiac adenylyl cyclase 6 reduces dilation and dysfunction of the pressure-overloaded heart. Biochem Biophys Res Commun. 2011;405:349-55 pubmed publisher
    Cardiac-directed adenylyl cyclase 6 (AC6) expression attenuates left ventricular (LV) hypertrophy and dysfunction in cardiomyopathy, but its effects in the pressure-overloaded heart are unknown...
  2. Premont R, Jacobowitz O, Iyengar R. Lowered responsiveness of the catalyst of adenylyl cyclase to stimulation by GS in heterologous desensitization: a role for adenosine 3',5'-monophosphate-dependent phosphorylation. Endocrinology. 1992;131:2774-84 pubmed
    ..The types 5 and 6 adenylyl cyclases are likely candidates for such regulation. ..
  3. Lavine N, Ethier N, Oak J, Pei L, Liu F, Trieu P, et al. G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. J Biol Chem. 2002;277:46010-9 pubmed
    ..The observation that several G protein-coupled receptors form stable complexes with their effectors suggests that this arrangement might be a general feature of G protein-coupled signal transduction. ..
  4. Yokoyama U, Minamisawa S, Katayama A, Tang T, Suzuki S, Iwatsubo K, et al. Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus. Circ Res. 2010;106:1882-92 pubmed publisher
    ..Our objectives were to examine whether AC isoforms play differential roles in DA vasodilation and IT. AC2 and AC6 were more highly expressed in rat DA than in the aorta during the perinatal period...
  5. Kaya F, Belin S, Diamantidis G, Fontes M. Ascorbic acid is a regulator of the intracellular cAMP concentration: old molecule, new functions?. FEBS Lett. 2008;582:3614-8 pubmed publisher
    ..In this work, we present kinetics data on the inhibitory effect of AA upon adenylate cyclase activity. The data show that this molecule acts as a competitive inhibitor of the enzyme, a finding that opens new pharmacological avenues. ..
  6. Rao R, Patel S, Hao C, Woodgett J, Harris R. GSK3beta mediates renal response to vasopressin by modulating adenylate cyclase activity. J Am Soc Nephrol. 2010;21:428-37 pubmed publisher
    ..In summary, GSK3beta inactivation or deletion reduces aquaporin 2 expression by modulating adenylate cyclase activity and cAMP generation, thereby impairing responses to vasopressin in the renal collecting duct. ..
  7. Visel A, Alvarez Bolado G, Thaller C, Eichele G. Comprehensive analysis of the expression patterns of the adenylate cyclase gene family in the developing and adult mouse brain. J Comp Neurol. 2006;496:684-97 pubmed
    ..This is suggestive of functional specialization. ..
  8. Wu C, DiJulio D, Jacobson K, McKnight G, Watson E. The contribution of AKAP5 in amylase secretion from mouse parotid acini. Am J Physiol Cell Physiol. 2010;298:C1151-8 pubmed publisher
    ..As a scaffolding protein, AKAP5 was found to coimmunoprecipitate with AC6, but not AC8...
  9. Yoshimura M, Cooper D. Cloning and expression of a Ca(2+)-inhibitable adenylyl cyclase from NCB-20 cells. Proc Natl Acad Sci U S A. 1992;89:6716-20 pubmed
    ..Its identification should permit a determination of the structural features that determine the mode of regulation of adenylyl cyclase by Ca2+. ..
  10. Edelhoff S, Villacres E, Storm D, Disteche C. Mapping of adenylyl cyclase genes type I, II, III, IV, V, and VI in mouse. Mamm Genome. 1995;6:111-3 pubmed situ hybridization (FISH): Adcy1 to Chr 11A2, Adcy2 to 13C1, Adcy3 to 12A-B, Adcy4 to 14D3, Adcy5 to 16B5, and Adcy6 to 15F...
  11. The E, Du P, Chang Y, Dai F, Wei C, Li J. Role of HSF1-upregulated AC6 in ameliorating heart failure in mice. Environ Toxicol Pharmacol. 2016;47:79-85 pubmed publisher
    ..However, its molecular mechanisms are yet to be further explained. Many studies have already verified that Adenylyl Cyclase 6 (AC6) can ameliorate heart failure, but it is still unknown whether or not the pathway HSF1 is involved in ..
  12. Chang C, Lee C, Hou W, Lin M, Lai H, Chien C, et al. Type VI adenylyl cyclase negatively regulates GluN2B-mediated LTD and spatial reversal learning. Sci Rep. 2016;6:22529 pubmed publisher
    The calcium-sensitive type VI adenylyl cyclase (AC6) is a membrane-bound adenylyl cyclase (AC) that converts ATP to cAMP under stimulation...
  13. Lee K, Hoey D, Spasic M, Tang T, Hammond H, Jacobs C. Adenylyl cyclase 6 mediates loading-induced bone adaptation in vivo. FASEB J. 2014;28:1157-65 pubmed publisher
    ..Previously we demonstrated that adenylyl cyclase 6 (AC6), a membrane-bound enzyme enriched in primary cilia of MLO-Y4 osteocyte-like cells, may play a role in ..
  14. Roos K, Bugaj V, Mironova E, Stockand J, Ramkumar N, Rees S, et al. Adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity. J Am Soc Nephrol. 2013;24:218-27 pubmed publisher
    ..In summary, these data suggest that adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity in the kidney...
  15. Kwon R, Temiyasathit S, Tummala P, Quah C, Jacobs C. Primary cilium-dependent mechanosensing is mediated by adenylyl cyclase 6 and cyclic AMP in bone cells. FASEB J. 2010;24:2859-68 pubmed publisher
    ..we identify a molecular mechanism linking primary cilia and bone cell mechanotransduction that involves adenylyl cyclase 6 (AC6) and cAMP...
  16. Guellich A, Gao S, Hong C, Yan L, Wagner T, Dhar S, et al. Effects of cardiac overexpression of type 6 adenylyl cyclase affects on the response to chronic pressure overload. Am J Physiol Heart Circ Physiol. 2010;299:H707-12 pubmed publisher
    Adenylyl cyclase (AC) type 5 (AC5) and AC type 6 (AC6) are the two major AC isoforms in the heart. Cardiac overexpression of AC6 has been shown to be protective in response to several interventions...
  17. Rieg T, Tang T, Murray F, Schroth J, Insel P, Fenton R, et al. Adenylate cyclase 6 determines cAMP formation and aquaporin-2 phosphorylation and trafficking in inner medulla. J Am Soc Nephrol. 2010;21:2059-68 pubmed publisher
    ..Here, we found that levels of AC6 mRNA, the most highly expressed AC isoform in the inner medulla, inversely correlate with fluid intake...
  18. Timofeyev V, Myers R, Kim H, Woltz R, Sirish P, Heiserman J, et al. Adenylyl cyclase subtype-specific compartmentalization: differential regulation of L-type Ca2+ current in ventricular myocytes. Circ Res. 2013;112:1567-76 pubmed publisher
    ..Because caveolae are found in most mammalian cells, the mechanism of ?- adrenergic receptor and AC compartmentalization may also be important for ?-adrenergic receptor signaling in other cell types. ..
  19. Meneray M, Lallier T. Differential expression of adenylyl cyclase mRNAs in lacrimal glands of NZB/NZW and NOD pre-autoimmune mice. Adv Exp Med Biol. 2002;506:41-9 pubmed
  20. Tang T, Gao M, Lai N, Firth A, Takahashi T, Guo T, et al. Adenylyl cyclase type 6 deletion decreases left ventricular function via impaired calcium handling. Circulation. 2008;117:61-9 pubmed
    ..The 2 ACs most abundantly expressed in cardiac myocytes are types 5 (AC5) and 6 (AC6), which have 65% amino acid homology...
  21. Hu C, Chandra R, Ge H, Pain J, Yan L, Babu G, et al. Adenylyl cyclase type 5 protein expression during cardiac development and stress. Am J Physiol Heart Circ Physiol. 2009;297:H1776-82 pubmed publisher
    Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from beta-adrenergic receptor stimulation...
  22. Rieg T, Tang T, Uchida S, Hammond H, Fenton R, Vallon V. Adenylyl cyclase 6 enhances NKCC2 expression and mediates vasopressin-induced phosphorylation of NKCC2 and NCC. Am J Pathol. 2013;182:96-106 pubmed publisher
    ..agonist (1-desamino-8-D-arginine vasopressin) in wild-type mice, is lacking in knockout mice for AC isoform 6 (AC6)...
  23. Klein C, Sunahara R, Hudson T, Heyduk T, Howlett A. Zinc inhibition of cAMP signaling. J Biol Chem. 2002;277:11859-65 pubmed
    ..33. The dose-response curve for Zn(2+) inhibition was identical for AC1, AC5, and AC6 as well as for the C441R mutant of AC5 whose defect appears to be in one of the catalytic metal binding sites...
  24. Roos K, Strait K, Raphael K, Blount M, Kohan D. Collecting duct-specific knockout of adenylyl cyclase type VI causes a urinary concentration defect in mice. Am J Physiol Renal Physiol. 2012;302:F78-84 pubmed publisher
    Collecting duct (CD) adenylyl cyclase VI (AC6) has been implicated in arginine vasopressin (AVP)-stimulated renal water reabsorption...
  25. Wang S, Lai H, Chiu Y, Ou R, Huang C, Chern Y. Regulation of type V adenylate cyclase by Ric8a, a guanine nucleotide exchange factor. Biochem J. 2007;406:383-8 pubmed
  26. Sabbatini M, D ALECY L, Lentz S, Tang T, Williams J. Adenylyl cyclase 6 mediates the action of cyclic AMP-dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation. J Physiol. 2013;591:3693-707 pubmed publisher
    ..Using RT-PCR, AC3, AC4, AC6, AC7 and AC9 were found to be expressed in the pancreas...
  27. Chien C, Wu Y, Lai H, Chen Y, Jiang S, Shih C, et al. Impaired water reabsorption in mice deficient in the type VI adenylyl cyclase (AC6). FEBS Lett. 2010;584:2883-90 pubmed publisher
    Adenylyl cyclase (AC) type VI (AC6) is a calcium-inhibitable enzyme which produces cAMP upon stimulation. Herein, we characterized the specific role of AC6 in the kidneys using two AC6-knockout mouse lines...
  28. Liu X, Li F, Sun S, Thangavel M, Kaminsky J, Balazs L, et al. Fibroblast-specific expression of AC6 enhances beta-adrenergic and prostacyclin signaling and blunts bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2010;298:L819-29 pubmed publisher
    ..In the present study, we overexpressed adenylyl cyclase 6 (AC6) in pulmonary fibroblasts and measured cAMP production and collagen synthesis...
  29. Rieg T, Gerasimova M, Murray F, Masuda T, Tang T, Rose M, et al. Natriuretic effect by exendin-4, but not the DPP-4 inhibitor alogliptin, is mediated via the GLP-1 receptor and preserved in obese type 2 diabetic mice. Am J Physiol Renal Physiol. 2012;303:F963-71 pubmed publisher
    ..These effects were absent in mice lacking the GLP-1R and independent of adenylyl cyclase 6. In comparison, parenteral application of the DPP-4 inhibitor alogliptin reduced plasma DPP-4 activity by 95%..
  30. Gao X, Sadana R, Dessauer C, Patel T. Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits. J Biol Chem. 2007;282:294-302 pubmed
    ..Moreover, Gbetagamma subunits derived from a source(s) other than G(i) are necessary for the full activation of hACVI by isoproterenol in intact cells. ..
  31. Ostrom R, Bundey R, Insel P. Nitric oxide inhibition of adenylyl cyclase type 6 activity is dependent upon lipid rafts and caveolin signaling complexes. J Biol Chem. 2004;279:19846-53 pubmed
    ..Because endothelial NO synthase (eNOS and NOS3), beta-adrenergic (betaAR) receptors, and AC6 all can localize in lipid raft/caveolin-rich microdomains, we sought to understand the role of lipid rafts in ..
  32. Suzuki Y, Shen T, Poyard M, Best Belpomme M, Hanoune J, Defer N. Expression of adenylyl cyclase mRNAs in the denervated and in the developing mouse skeletal muscle. Am J Physiol. 1998;274:C1674-85 pubmed
    ..Four isoforms of AC (AC2, AC6, AC7, and AC9) were detected by Northern blot analysis in gastrocnemius muscle, AC9 being the most abundant...
  33. Cai W, Du A, Feng K, Zhao X, Qian L, Ostrom R, et al. Adenylyl cyclase 6 activation negatively regulates TLR4 signaling through lipid raft-mediated endocytosis. J Immunol. 2013;191:6093-100 pubmed publisher
    ..7) and bone marrow-derived macrophages when stimulated with LPS. We further show that the AC6 isoform plays a key role in negative regulation of TLR4 signaling by promoting protein degradation...
  34. Kittikulsuth W, Stuart D, Van Hoek A, Stockand J, Bugaj V, Mironova E, et al. Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure. Am J Physiol Renal Physiol. 2014;306:F597-607 pubmed publisher
    ..Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3/AC6 KO mice had ..
  35. Hopp K, Hommerding C, Wang X, Ye H, Harris P, Torres V. Tolvaptan plus pasireotide shows enhanced efficacy in a PKD1 model. J Am Soc Nephrol. 2015;26:39-47 pubmed publisher
    ..Compounds such as tolvaptan and pasireotide, which indirectly reduce adenylyl cyclase 6 (AC6) activity, have hence proven effective in slowing cyst progression...
  36. Rees S, Kittikulsuth W, Roos K, Strait K, Van Hoek A, Kohan D. Adenylyl cyclase 6 deficiency ameliorates polycystic kidney disease. J Am Soc Nephrol. 2014;25:232-7 pubmed publisher
    ..In contrast, coincident collecting duct-specific knockout of polycystin-1 and AC6 (also homozygous for the floxed ADCY6 gene) markedly decreased kidney size and cystogenesis, improved renal function, reduced activation of the B-Raf/..
  37. Mahavadi S, Nalli A, Kumar D, Hu W, Kuemmerle J, Grider J, et al. Cytokine-induced iNOS and ERK1/2 inhibit adenylyl cyclase type 5/6 activity and stimulate phosphodiesterase 4D5 activity in intestinal longitudinal smooth muscle. Am J Physiol Cell Physiol. 2014;307:C402-11 pubmed publisher
    ..The changes in the cAMP/PKA signaling and smooth muscle relaxation contribute to colonic dysmotility during inflammation. ..
  38. Nicol X, Bennis M, Ishikawa Y, Chan G, Repérant J, Storm D, et al. Role of the calcium modulated cyclases in the development of the retinal projections. Eur J Neurosci. 2006;24:3401-14 pubmed
    ..The specificity of AC1's action is linked to its cellular localization in the RGCs and to its distinctive functional profile, compared with the other cyclases expressed in the same cells. ..
  39. Pinto C, Reif G, Nivens E, White C, Wallace D. Calmodulin-sensitive adenylyl cyclases mediate AVP-dependent cAMP production and Cl- secretion by human autosomal dominant polycystic kidney cells. Am J Physiol Renal Physiol. 2012;303:F1412-24 pubmed publisher
    ..We suggest that a compensatory response to decreased Ca(2+) in ADPKD cells switches V2R coupling from Ca(2+)-inhibited ACs 5/6 to Ca(2+)/CaM-stimulated AC3, to mitigate high cAMP levels in response to continuous AVP stimulation. ..
  40. Chien C, Lin M, Lai H, Wu Y, Chang C, Chen H, et al. Lack of type VI adenylyl cyclase (AC6) leads to abnormal sympathetic tone in neonatal mice. Exp Neurol. 2013;248:10-5 pubmed publisher
    ..We demonstrate herein that AC6 existed in tyrosine hydroxylase-positive rostral ventrolateral medulla neurons in the brainstem...