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Gene Review

CYR1  -  adenylate cyclase

Saccharomyces cerevisiae S288c

Synonyms: ATP pyrophosphate-lyase, Adenylate cyclase, Adenylyl cyclase, CDC35, FIL1, ...
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Disease relevance of CYR1

  • Mixing a crude extract from the E. coli transformant carrying CYR1 with a crude extract from cells carrying RAS2 reconstituted the GTP-dependent adenylate cyclase [1].
  • Long-term increases in neurotransmitter release from neuronal cells expressing a constitutively active adenylate cyclase from a herpes simplex virus type 1 vector [2].
  • The crystal structure of the class IV adenylyl cyclase (AC) from Yersinia pestis (Yp) is reported at 1.9 A resolution [3].
  • To separate the signaling and desensitization of beta2AR, which mediates stimulation of adenylyl cyclase, S49 lymphoma cys- cells that lack the alpha subunit of Gs were used [4].
  • Dermal fibroblasts had higher AC activity and intracellular cAMP levels than the colon cancer lines (p less than 0.05) [5].

High impact information on CYR1

  • Adenylyl cyclase activity in membranes from cells that lacked CAP was not stimulated by RAS2 proteins in vitro [6].
  • These results demonstrate that SRV2 protein is required for RAS-activated adenylate cyclase activity, but that it participates in other essential cellular functions as well [7].
  • Adenylyl cyclase from S. cerevisiae contains at least two subunits, a 200 kd catalytic subunit and a subunit with an apparent molecular size of 70 kd, which we now call CAP (cyclase-associated protein) [6].
  • Mutants lacking CAP had four additional phenotypes that appear to be unrelated to effects of the RAS/adenylyl cyclase pathway: the inability to grow on rich medium (YPD), temperature sensitivity on minimal medium, sensitivity to nitrogen starvation, and a swollen cell morphology [6].
  • Estrogen was found to lead to higher steady-state levels of adenylate cyclase mRNA but not to affect the expression of the RAS1 and RAS2 genes, although these can also alter the intracellular cAMP level [8].

Chemical compound and disease context of CYR1


Biological context of CYR1


Anatomical context of CYR1

  • Here we show that mutations in CYR1 and SCH9 also extend the replicative life span of individual yeast mother cells [12].
  • The relative amount of membrane-bound adenylate cyclase was drastically reduced in cdc25 ts membranes when subjected to the restrictive temperature, while no significant change was observed in the wild type [13].
  • These data suggest that Cdc25 might not be required in certain conditions for the guanine nucleotide exchange reaction in Ras and that it might be implicated in anchoring the Ras/adenylate cyclase system to the plasma membrane [13].
  • In this investigation, we have studied whether the posttranslational processing of Ki- and Ha-ras p21s is critical for their stimulation of yeast adenylate cyclase in a cell-free system [14].
  • The data suggest an interaction of CAP with adenylyl cyclase in Dictyostelium and an influence on signaling pathways directly as well as through its function as a regulatory component of the cytoskeleton [15].

Associations of CYR1 with chemical compounds

  • Screening of approximately 13,000 mutagenized colonies for galactose-dependent growth at a high temperature (37 degrees) yielded six temperature-sensitive ras2 (ras2ts) mutations and one temperature-sensitive cyr1 (cyr1ts) mutation that can be suppressed by overexpression or increased dosage of RAS2 [16].
  • It is also shown that 6-deoxyglucose can activate adenylate cyclase in the absence of CDC25 gene product [13].
  • The mutation predicts the replacement of threonine by isoleucine at position 1651 of yeast adenylate cyclase [17].
  • Incubation of wild-type membranes with lysophosphatidylinositol, lysophosphatidylserine, or lysophosphatidylcholine stimulated adenylyl cyclase activity in the absence and presence of RAS between 2-10-fold depending upon the individual lipid [18].
  • An inhibitor of mammalian adenylate cyclase, MDL-12330A, was tested in combination with azoles; a synergistic effect was observed against azole-susceptible and -resistant strains of C. albicans and five of six non-C. albicans Candida species [19].

Physical interactions of CYR1


Enzymatic interactions of CYR1


Regulatory relationships of CYR1


Other interactions of CYR1


Analytical, diagnostic and therapeutic context of CYR1


  1. Reconstitution of the GTP-dependent adenylate cyclase from products of the yeast CYR1 and RAS2 genes in Escherichia coli. Uno, I., Mitsuzawa, H., Matsumoto, K., Tanaka, K., Oshima, T., Ishikawa, T. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  2. Long-term increases in neurotransmitter release from neuronal cells expressing a constitutively active adenylate cyclase from a herpes simplex virus type 1 vector. Geller, A.I., During, M.J., Haycock, J.W., Freese, A., Neve, R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  3. 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]
  4. Relationship between the G protein signaling and homologous desensitization of G protein-coupled receptors. Barak, L.S., Gilchrist, J., Becker, J.M., Kim, K.M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  5. Adenylate cyclase activity and cyclic adenosine monophosphate levels in colon cancer lines and dermal fibroblasts and the effects of cholera toxin and epidermal growth factor. Nelson, R.L., Holian, O. Journal of surgical oncology. (1988) [Pubmed]
  6. Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein. Field, J., Vojtek, A., Ballester, R., Bolger, G., Colicelli, J., Ferguson, K., Gerst, J., Kataoka, T., Michaeli, T., Powers, S. Cell (1990) [Pubmed]
  7. SRV2, a gene required for RAS activation of adenylate cyclase in yeast. Fedor-Chaiken, M., Deschenes, R.J., Broach, J.R. Cell (1990) [Pubmed]
  8. Estrogen can regulate the cell cycle in the early G1 phase of yeast by increasing the amount of adenylate cyclase mRNA. Tanaka, S., Hasegawa, S., Hishinuma, F., Kurata, S. Cell (1989) [Pubmed]
  9. Characterization of mammalian Gs-alpha proteins expressed in yeast. Stadel, J.M., Ecker, D.J., Powers, D.A., Marsh, J., Hoyle, K., Gross, M., Minnich, M.D., Butt, T.R., Crooke, S.T. J. Recept. Res. (1994) [Pubmed]
  10. Identification of the domain of Saccharomyces cerevisiae adenylate cyclase associated with the regulatory function of RAS products. Uno, I., Mitsuzawa, H., Tanaka, K., Oshima, T., Ishikawa, T. Mol. Gen. Genet. (1987) [Pubmed]
  11. The adenylate cyclase/protein kinase cascade regulates entry into meiosis in Saccharomyces cerevisiae through the gene IME1. Matsuura, A., Treinin, M., Mitsuzawa, H., Kassir, Y., Uno, I., Simchen, G. EMBO J. (1990) [Pubmed]
  12. Chronological aging-independent replicative life span regulation by Msn2/Msn4 and Sod2 in Saccharomyces cerevisiae. Fabrizio, P., Pletcher, S.D., Minois, N., Vaupel, J.W., Longo, V.D. FEBS Lett. (2004) [Pubmed]
  13. Activation of adenylate cyclase in cdc25 mutants of Saccharomyces cerevisiae. Pardo, L.A., Lazo, P.S., Ramos, S. FEBS Lett. (1993) [Pubmed]
  14. The posttranslational processing of ras p21 is critical for its stimulation of yeast adenylate cyclase. Horiuchi, H., Kaibuchi, K., Kawamura, M., Matsuura, Y., Suzuki, N., Kuroda, Y., Kataoka, T., Takai, Y. Mol. Cell. Biol. (1992) [Pubmed]
  15. The cyclase-associated protein CAP as regulator of cell polarity and cAMP signaling in Dictyostelium. Noegel, A.A., Blau-Wasser, R., Sultana, H., Müller, R., Israel, L., Schleicher, M., Patel, H., Weijer, C.J. Mol. Biol. Cell (2004) [Pubmed]
  16. Isolation and characterization of temperature-sensitive mutations in the RAS2 and CYR1 genes of Saccharomyces cerevisiae. Mitsuzawa, H., Uno, I., Oshima, T., Ishikawa, T. Genetics (1989) [Pubmed]
  17. Suppression of defective RAS1 and RAS2 functions in yeast by an adenylate cyclase activated by a single amino acid change. De Vendittis, E., Vitelli, A., Zahn, R., Fasano, O. EMBO J. (1986) [Pubmed]
  18. Stimulation of yeast adenylyl cyclase activity by lysophospholipids and fatty acids. Implications for the regulation of Ras/effector function by lipids. Resnick, R.J., Tomáska, L. J. Biol. Chem. (1994) [Pubmed]
  19. Cyclic AMP signaling pathway modulates susceptibility of candida species and Saccharomyces cerevisiae to antifungal azoles and other sterol biosynthesis inhibitors. Jain, P., Akula, I., Edlind, T. Antimicrob. Agents Chemother. (2003) [Pubmed]
  20. RA domain-mediated interaction of Cdc35 with Ras1 is essential for increasing cellular cAMP level for Candida albicans hyphal development. Fang, H.M., Wang, Y. Mol. Microbiol. (2006) [Pubmed]
  21. The SH3 domain of the S. cerevisiae Cdc25p binds adenylyl cyclase and facilitates Ras regulation of cAMP signalling. Mintzer, K.A., Field, J. Cell. Signal. (1999) [Pubmed]
  22. Sgt1p contributes to cyclic AMP pathway activity and physically interacts with the adenylyl cyclase Cyr1p/Cdc35p in budding yeast. Dubacq, C., Guerois, R., Courbeyrette, R., Kitagawa, K., Mann, C. Eukaryotic Cell (2002) [Pubmed]
  23. Rapamycin specifically interferes with the developmental response of fission yeast to starvation. Weisman, R., Choder, M., Koltin, Y. J. Bacteriol. (1997) [Pubmed]
  24. Anti-Cdc25 antibodies inhibit guanyl nucleotide-dependent adenylyl cyclase of Saccharomyces cerevisiae and cross-react with a 150-kilodalton mammalian protein. Gross, E., Marbach, I., Engelberg, D., Segal, M., Simchen, G., Levitzki, A. Mol. Cell. Biol. (1992) [Pubmed]
  25. Interactions between adenylate cyclase and the yeast GTPase-activating protein IRA1. Mitts, M.R., Bradshaw-Rouse, J., Heideman, W. Mol. Cell. Biol. (1991) [Pubmed]
  26. In yeast, RAS proteins are controlling elements of adenylate cyclase. Toda, T., Uno, I., Ishikawa, T., Powers, S., Kataoka, T., Broek, D., Cameron, S., Broach, J., Matsumoto, K., Wigler, M. Cell (1985) [Pubmed]
  27. A new RAS mutation that suppresses the CDC25 gene requirement for growth of Saccharomyces cerevisiae. Camonis, J.H., Jacquet, M. Mol. Cell. Biol. (1988) [Pubmed]
  28. Activation state of the Ras2 protein and glucose-induced signaling in Saccharomyces cerevisiae. Colombo, S., Ronchetti, D., Thevelein, J.M., Winderickx, J., Martegani, E. J. Biol. Chem. (2004) [Pubmed]
  29. Suppressors of the ras2 mutation of Saccharomyces cerevisiae. Cannon, J.F., Gibbs, J.B., Tatchell, K. Genetics (1986) [Pubmed]
  30. A TY1 element is inserted in the CYR1 control region of Saccharomyces cerevisiae strain AB320. Lenzen, G., Masson, P., Jacquemin, J.M., Danchin, A. FEBS Lett. (1987) [Pubmed]
  31. Properties of the SDC25 C-domain, a GDP to GTP exchange factor of RAS proteins and in vitro modulation of adenylyl cyclase. Créchet, J.B., Poullet, P., Bernardi, A., Fasano, O., Parmeggiani, A. J. Biol. Chem. (1993) [Pubmed]
  32. Molecular cloning of the tsm0185 gene responsible for adenylate cyclase activity in Saccharomyces cerevisiae. Masson, P., Jacquemin, J.M., Culot, M. Ann. Microbiol. (Paris) (1984) [Pubmed]
  33. Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Field, J., Nikawa, J., Broek, D., MacDonald, B., Rodgers, L., Wilson, I.A., Lerner, R.A., Wigler, M. Mol. Cell. Biol. (1988) [Pubmed]
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