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Gene Review

CNA1  -  calcineurin catalytic subunit A

Saccharomyces cerevisiae S288c

Synonyms: CMP1, Calcineurin A1, Calmodulin-binding protein 1, L9753.6, Serine/threonine-protein phosphatase 2B catalytic subunit A1, ...
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Disease relevance of CNA1


High impact information on CNA1

  • It is a heterodimeric protein consisting of a catalytic subunit calcineurin A, which contains an active site dinuclear metal center, and a tightly associated, myristoylated, Ca(2+)-binding subunit, calcineurin B. The primary sequence of both subunits and heterodimeric quaternary structure is highly conserved from yeast to mammals [2].
  • Genetic evidence supports a model in which immunophilin-drug complexes inhibit calcineurin to prevent growth at 37 degrees C. The gene encoding the C. neoformans calcineurin A catalytic subunit was cloned and disrupted by homologous recombination [3].
  • Introduction of the wild-type calcineurin A gene complemented these growth defects and restored virulence [3].
  • Double mutant calcineurin A subunits (Y377F, W388C CMP1 and Y419F, W430C CMP2) confer resistance to CsA, to FK506 and to CsA plus FK506 [4].
  • When introduced into the CMP1 subunit, the FK506 resistance mutation (W388C) blocks binding by FKBP12-FK506, but not by cyclophilin A-CsA [4].

Biological context of CNA1


Anatomical context of CNA1


Associations of CNA1 with chemical compounds

  • Co-expression of CsA-resistant and FK506-resistant calcineurin A subunits confers resistance to CsA and to FK506 but not to CsA plus FK506 [4].
  • Mutations in calcineurin A or B subunits or the inhibitory compounds FK506 and cyclosporin A restore growth of pmc1 mutants in high Ca2+ media [11].
  • In vitro, both wild-type and CNB1-G2A mutant proteins formed complexes with both cyclophilin A-cyclosporin A (CsA) and FKBP12-FK506 that contained calcineurin A. Interestingly, expression of the nonmyristoylated CNB1-G2A mutant protein rendered yeast cells partially resistant to the immunosuppressant CsA, but not to FK506 [12].
  • Consistent with this observation, tolerance to fluconazole was modulated by calcium ions or by the expression of a calcineurin A derivative autoactivated by the removal of its C-terminal inhibitory domain [13].

Physical interactions of CNA1


Other interactions of CNA1

  • Cna1p and Cna2p, the products of two yeast genes encoding the catalytic (A) subunits of calcineurin, were major constituents of the purified fraction [16].
  • We show that six substitutions (R177G, F211S, S232F, D258V, L259P, and A262P) affect the stability of calcineurin and that two substitutions (V385D and M400R) disrupt the interaction between Cna1p and the calcineurin regulatory subunit Cnb1p [5].
  • Interestingly, both CsA and FK506 disrupt this interaction, whereas binding of Cna1 to calmodulin remains unaffected [17].
  • The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the yeast spindle pole body [18].
  • PCR analysis with primers specific for serotype A or D alleles of the CNA1, CLA4, and GPA1 genes revealed that both alleles are often present in serotype AD strains [19].


  1. Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of Saccharomyces cerevisiae. Parent, S.A., Nielsen, J.B., Morin, N., Chrebet, G., Ramadan, N., Dahl, A.M., Hsu, M.J., Bostian, K.A., Foor, F. J. Gen. Microbiol. (1993) [Pubmed]
  2. Calcineurin: form and function. Rusnak, F., Mertz, P. Physiol. Rev. (2000) [Pubmed]
  3. Calcineurin is required for virulence of Cryptococcus neoformans. Odom, A., Muir, S., Lim, E., Toffaletti, D.L., Perfect, J., Heitman, J. EMBO J. (1997) [Pubmed]
  4. Targets of immunophilin-immunosuppressant complexes are distinct highly conserved regions of calcineurin A. Cardenas, M.E., Muir, R.S., Breuder, T., Heitman, J. EMBO J. (1995) [Pubmed]
  5. Identification of a novel region critical for calcineurin function in vivo and in vitro. Jiang, B., Cyert, M.S. J. Biol. Chem. (1999) [Pubmed]
  6. Involvement of thioredoxin peroxidase type II (Ahp1p) of Saccharomyces cerevisiae in Mn2+ homeostasis. Farcasanu, I.C., Hirata, D., Tsuchiya, E., Mizuta, K., Miyakawa, T. Biosci. Biotechnol. Biochem. (1999) [Pubmed]
  7. Antisense repression in Cryptococcus neoformans as a laboratory tool and potential antifungal strategy. Gorlach, J.M., McDade, H.C., Perfect, J.R., Cox, G.M. Microbiology (Reading, Engl.) (2002) [Pubmed]
  8. AtBAG6, a novel calmodulin-binding protein, induces programmed cell death in yeast and plants. Kang, C.H., Jung, W.Y., Kang, Y.H., Kim, J.Y., Kim, D.G., Jeong, J.C., Baek, D.W., Jin, J.B., Lee, J.Y., Kim, M.O., Chung, W.S., Mengiste, T., Koiwa, H., Kwak, S.S., Bahk, J.D., Lee, S.Y., Nam, J.S., Yun, D.J., Cho, M.J. Cell Death Differ. (2006) [Pubmed]
  9. Glucose-independent inhibition of yeast plasma-membrane H+-ATPase by calmodulin antagonists. Romero, I., Maldonado, A.M., Eraso, P. Biochem. J. (1997) [Pubmed]
  10. Pcp1p, an Spc110p-related calmodulin target at the centrosome of the fission yeast Schizosaccharomyces pombe. Flory, M.R., Morphew, M., Joseph, J.D., Means, A.R., Davis, T.N. Cell Growth Differ. (2002) [Pubmed]
  11. Calcineurin-dependent growth control in Saccharomyces cerevisiae mutants lacking PMC1, a homolog of plasma membrane Ca2+ ATPases. Cunningham, K.W., Fink, G.R. J. Cell Biol. (1994) [Pubmed]
  12. Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae. Zhu, D., Cardenas, M.E., Heitman, J. J. Biol. Chem. (1995) [Pubmed]
  13. Calcineurin A of Candida albicans: involvement in antifungal tolerance, cell morphogenesis and virulence. Sanglard, D., Ischer, F., Marchetti, O., Entenza, J., Bille, J. Mol. Microbiol. (2003) [Pubmed]
  14. Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. Cardenas, M.E., Hemenway, C., Muir, R.S., Ye, R., Fiorentino, D., Heitman, J. EMBO J. (1994) [Pubmed]
  15. Identification and molecular characterization of the calmodulin-binding subunit gene (CMP1) of protein phosphatase 2B from Saccharomyces cerevisiae. An alpha-factor inducible gene. Ye, R.R., Bretscher, A. Eur. J. Biochem. (1992) [Pubmed]
  16. Regulatory subunit (CNB1 gene product) of yeast Ca2+/calmodulin-dependent phosphoprotein phosphatases is required for adaptation to pheromone. Cyert, M.S., Thorner, J. Mol. Cell. Biol. (1992) [Pubmed]
  17. The interaction between the catalytic A subunit of calcineurin and its autoinhibitory domain, in the yeast two-hybrid system, is disrupted by cyclosporin A and FK506. Chaudhuri, B., Hämmerle, M., Fürst, P. FEBS Lett. (1995) [Pubmed]
  18. The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the yeast spindle pole body. Zhu, G., Davis, T.N. Biochim. Biophys. Acta (1998) [Pubmed]
  19. Serotype AD strains of Cryptococcus neoformans are diploid or aneuploid and are heterozygous at the mating-type locus. Lengeler, K.B., Cox, G.M., Heitman, J. Infect. Immun. (2001) [Pubmed]
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