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Gene Review

ACE2  -  Ace2p

Saccharomyces cerevisiae S288c

Synonyms: L3123, L9606.10, Metallothionein expression activator, YLR131C
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Disease relevance of ACE2

  • Furthermore, ligand blot assay showed that the recombinant S1 could react with ACE2, the receptor of SARS-CoV [1].
  • Inactivation of C. glabrata ACE2 does not result in attenuation but, conversely, in a strain that is hypervirulent in a murine model of invasive candidiasis [2].
  • Then, approx. 59 mg l(-1) of ace2 was overexpressed in Escherichia coli BL21 [3].
  • We also show that Ace2 is required for filamentation in response to low oxygen concentrations (hypoxia) [4].

High impact information on ACE2

  • Other genes in the second cluster, which are required for G1-S progression, are regulated by the MBF complex independently of Sep1p and Ace2p [5].
  • The forkhead protein Sep1p regulates mitotic genes in the first cluster, including Ace2p, which activates transcription in the second cluster during the M-G1 transition and cytokinesis [5].
  • Daughter-specific expression is due to Cbk1/Mob2-dependent activation and localization of the Ace2 transcription factor to the daughter nucleus [6].
  • SWI5 is a transcriptional activator of the HO endonuclease gene, whereas ACE2 is not [7].
  • Chimeric SWI5/ACE2 protein fusion experiments suggest that promoter specificity resides in a domain distinct from the zinc finger domain [7].

Biological context of ACE2

  • A genetic screen was conducted to identify suppressor mutations which allow CTS1 expression in the absence of the Ace2p activator [8].
  • Analysis of CTS1 promoter fragments inserted into a heterologous promoter identify a sequence 90 bp away from the Ace2p binding sites which is required to prevent activation by Swi5p through these binding sites [8].
  • The yeast transcription factors Ace2p and Swi5p regulate the expression of several target genes involved in mating type switching, exit from mitosis and cell wall function [9].
  • Additionally, these mutants show altered colony morphology, cell separation defects, and reduced CTS1 expression, phenotypes also seen by mutating the Ace2 transcription factor [10].
  • We show that an ACE2 multicopy plasmid suppresses the latter three defects of RAM network mutations, demonstrating that Ace2 is downstream of the RAM network and suggesting that these phenotypes are caused by reduced expression of Ace2 target genes [10].

Anatomical context of ACE2

  • Deletion of ACE2 produces daughter cells that proceed through G1 at the same rate as mother cells, whereas a mutant Ace2 protein that is not restricted to daughter cells delays G1 equally in both mothers and daughters [11].

Associations of ACE2 with chemical compounds

  • In animals rendered temporarily neutropenic by cyclophosphamide treatment, the C. glabrata ace2 null mutant was confirmed as hypervirulent: it led to early terminal illness and kidney, brain, and lung fungal burdens substantially and significantly larger than those in controls [12].
  • This is supported by the observation that deleting ace2 results in increased resistance to antimycin A, a drug that inhibits respiration [4].
  • In contrast, genes required for acetyl-coenzyme A and lipid metabolism are upregulated in an ace2 deletion mutant grown predominantly as yeast cells but are downregulated in hyphae [4].

Regulatory relationships of ACE2

  • Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae [13].
  • This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner [14].
  • In yeast, Hym1p plays a role in cellular morphogenesis and also promotes the daughter cell-specific localization of the Ace2p transcription factor [15].
  • Many of these genes are regulated by a transcriptional cascade involving two transcription factors: the forkhead protein Sep1p which activates the zinc finger protein Ace2p [16].

Other interactions of ACE2

  • Role of negative regulation in promoter specificity of the homologous transcriptional activators Ace2p and Swi5p [8].
  • Like Cts1p and Scw11p, the two new Ace2p targets are associated with cell wall metabolism [9].
  • Experiments examining budding patterns and sedimentation rates both show that Ace2 and Cbk1 have independent functions in addition to their common pathway in transcription of genes such as CTS1 [10].
  • Here we show that the forkhead protein Fkh2 is a component of SFF and is essential for ternary complex formation on the SWI5 and ACE2 promoters [17].
  • We have isolated a gene, designated ACE2, which when present on a high-copy-number plasmid suppresses the copper-sensitive phenotype of an ace1-deletion strain [18].


  1. Modification of SARS-CoV S1 gene render expression in Pichia pastoris. Lu, H., Yang, G., Fei, X., Guo, H., Tan, Y., Chen, H., Guo, A. Virus Genes (2006) [Pubmed]
  2. Inactivation of transcription factor gene ACE2 in the fungal pathogen Candida glabrata results in hypervirulence. Kamran, M., Calcagno, A.M., Findon, H., Bignell, E., Jones, M.D., Warn, P., Hopkins, P., Denning, D.W., Butler, G., Rogers, T., Mühlschlegel, F.A., Haynes, K. Eukaryotic Cell (2004) [Pubmed]
  3. Construction of a yeast one-hybrid system with the xylanase2 promoter from Trichoderma reesei to isolate transcriptional activators. Liu, J., Sun, S.Y., Wang, T.H. Lett. Appl. Microbiol. (2004) [Pubmed]
  4. Candida albicans Transcription Factor Ace2 Regulates Metabolism and Is Required for Filamentation in Hypoxic Conditions. Mulhern, S.M., Logue, M.E., Butler, G. Eukaryotic Cell (2006) [Pubmed]
  5. Periodic gene expression program of the fission yeast cell cycle. Rustici, G., Mata, J., Kivinen, K., Lió, P., Penkett, C.J., Burns, G., Hayles, J., Brazma, A., Nurse, P., Bähler, J. Nat. Genet. (2004) [Pubmed]
  6. Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Colman-Lerner, A., Chin, T.E., Brent, R. Cell (2001) [Pubmed]
  7. Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. Dohrmann, P.R., Butler, G., Tamai, K., Dorland, S., Greene, J.R., Thiele, D.J., Stillman, D.J. Genes Dev. (1992) [Pubmed]
  8. Role of negative regulation in promoter specificity of the homologous transcriptional activators Ace2p and Swi5p. Dohrmann, P.R., Voth, W.P., Stillman, D.J. Mol. Cell. Biol. (1996) [Pubmed]
  9. Overlapping and distinct roles of the duplicated yeast transcription factors Ace2p and Swi5p. Doolin, M.T., Johnson, A.L., Johnston, L.H., Butler, G. Mol. Microbiol. (2001) [Pubmed]
  10. ACE2, CBK1, and BUD4 in budding and cell separation. Voth, W.P., Olsen, A.E., Sbia, M., Freedman, K.H., Stillman, D.J. Eukaryotic Cell (2005) [Pubmed]
  11. ACE2 is required for daughter cell-specific G1 delay in Saccharomyces cerevisiae. Laabs, T.L., Markwardt, D.D., Slattery, M.G., Newcomb, L.L., Stillman, D.J., Heideman, W. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Different consequences of ACE2 and SWI5 gene disruptions for virulence of pathogenic and nonpathogenic yeasts. MacCallum, D.M., Findon, H., Kenny, C.C., Butler, G., Haynes, K., Odds, F.C. Infect. Immun. (2006) [Pubmed]
  13. Regulated nuclear localisation of the yeast transcription factor Ace2p controls expression of chitinase (CTS1) in Saccharomyces cerevisiae. O'Conallain, C., Doolin, M.T., Taggart, C., Thornton, F., Butler, G. Mol. Gen. Genet. (1999) [Pubmed]
  14. Identification of novel Saccharomyces cerevisiae proteins with nuclear export activity: cell cycle-regulated transcription factor ace2p shows cell cycle-independent nucleocytoplasmic shuttling. Jensen, T.H., Neville, M., Rain, J.C., McCarthy, T., Legrain, P., Rosbash, M. Mol. Cell. Biol. (2000) [Pubmed]
  15. Hym1p affects cell cycle progression in Saccharomyces cerevisiae. Bogomolnaya, L.M., Pathak, R., Guo, J., Cham, R., Aramayo, R., Polymenis, M. Curr. Genet. (2004) [Pubmed]
  16. A transcriptional pathway for cell separation in fission yeast. Bähler, J. Cell Cycle (2005) [Pubmed]
  17. The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. Pic, A., Lim, F.L., Ross, S.J., Veal, E.A., Johnson, A.L., Sultan, M.R., West, A.G., Johnston, L.H., Sharrocks, A.D., Morgan, B.A. EMBO J. (2000) [Pubmed]
  18. ACE2, an activator of yeast metallothionein expression which is homologous to SWI5. Butler, G., Thiele, D.J. Mol. Cell. Biol. (1991) [Pubmed]
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