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SNF1  -  AMP-activated serine/threonine-protein...

Saccharomyces cerevisiae S288c

Synonyms: CAT1, CCR1, Carbon catabolite-derepressing protein kinase, D8035.20, GLC2, ...
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Disease relevance of SNF1

  • Together, these observations suggest that metabolic alterations mediated by SNF1 are an important component of innate antiviral defenses and that the inactivation of ADK and SNF1 by the geminivirus proteins represents a dual strategy to counter this defense [1].
  • In yeast, SNF1 is one of the main regulators in the shift from fermentation to aerobic metabolism; AMPK, its mammalian counterpart, is a master metabolic regulator involved in a variety of metabolic disorders such as diabetes and obesity [2].
  • A snf1 null mutant is sensitive to heat stress and starvation and fails to accumulate glycogen during growth in rich medium [3].

High impact information on SNF1


Biological context of SNF1

  • The predicted kinase domain of NPK5 is 65% identical in terms of amino acid sequence to that of the SNF1 serine/threonine protein kinase of Saccharomyces cerevisiae, which plays a central role in catabolite repression in yeast cells [6].
  • A genetic screen revealed that two genes involved in autophagy, APG1 and APG13, may be regulated by SNF1 [7].
  • Elm1p also activated the purified SNF1 complex, and this correlated with phosphorylation of Thr210 in the activation loop [8].
  • In addition, derepression of cell cycle genes and signalling via the cAMP-PKA pathway appears to depend upon SNF1 activity during growth on galactose [9].
  • Recent data suggest that the plant SNF1-related kinases (SnRK1 family) are key enzymes implicated in the regulation of carbohydrate and lipid metabolism [10].

Anatomical context of SNF1

  • No peroxisomes were detected in snf1 and snf4 mutants by immunogold labelling as well as by immunofluorescence [11].
  • To examine glucose repression of invasive growth more broadly, we performed genome-wide microarray expression analysis in wild-type cells growing on glucose and galactose, and snf1 Delta cells on galactose [9].
  • In liver cells, pharmacological activation by 5-amino-4-imidazolecarboxamide riboside (AICAR) of AMP-activated protein kinase (AMPK), the mammalian homologue of the yeast SNF1 kinase complex, inhibits the effects of glucose, suggesting a key signaling role for this kinase [12].
  • The binding affinities of various mutant insulin analogues correlated well with their capacities to activate glycogen synthase and SNF1 kinase in glucose-induced yeast spheroplasts, the ranking of their relative efficacies in yeast and in isolated rat adipocytes being similar [13].
  • These results show that in beta cell lines the AMP-activated protein kinase, like its yeast homologue the SNF1 complex, can respond to the level of glucose in the medium, and may be involved in regulating insulin release [14].

Associations of SNF1 with chemical compounds

  • The SSN3 and SSN8 genes of Saccharomyces cerevisiae were identified by mutations that suppress a defect in SNF1, a protein kinase required for release from glucose repression [15].
  • Cells lacking the SNF1 gene cannot express glucose-repressible genes and do not accumulate the storage polysaccharide glycogen [16].
  • Expression and regulation of the AMP-activated protein kinase-SNF1 (sucrose non-fermenting 1) kinase complexes in yeast and mammalian cells: studies using chimaeric catalytic subunits [17].
  • The sequence relationships between the mammalian 5'-AMP-activated protein kinase and yeast Snf1p extend to the subunit proteins consistent with conservation of the functional roles of these polypeptides in cellular regulation by this family of metabolite-sensing protein kinases [18].
  • Increased gene dosage of SIP1 rescued the ethanol growth defect observed in cells expressing Sip1 as their only beta subunit and increased the in vitro activity of Snf1 kinase purified from these cells [19].
  • Glucose-mediated regulation of Snf1 activation loop dephosphorylation is controlled by changes in the ability of the Snf1 activation loop to act as a substrate for Glc7 [20].
  • Mutations at several sites relieved glucose inhibition of SNF1, as judged by catalytic activity, phosphorylation of the activation-loop Thr-210, and growth assays, although analogs of the severe human mutations R531G/Q had little effect [21].

Physical interactions of SNF1

  • Finally, MSN3 physically interacts with the SNF1 protein kinase, as assayed by a two-hybrid system and by in vitro binding studies [22].
  • It is also affected by the HAP2/3/4 transcription factor complex and by SNF1 and SSN6 [23].
  • Examination of the protein composition of the purified Snf1 enzyme complexes indicated that the Sip1 protein was present in substoichiometric levels [19].
  • Furthermore, Gts1p bound to subunits of Snf1 kinase, whereas it did not bind to DNA [24].
  • One molecular function of the Snf1 complex is deactivation by phosphorylation of the general glucose repressor Mig1 [25].

Enzymatic interactions of SNF1

  • Together, our data are consistent with a model in which Reg1p and Reg2p control the activity of PP1 toward substrates that are phosphorylated by the Snf1p kinase [26].
  • In immune complex assays of Snf1, coprecipitating Mig1 is phosphorylated in a Snf1-dependent reaction [27].
  • We have investigated whether the corresponding counterpart of filamentous fungi-the Cre1 protein-is also phosphorylated by Snf1 [28].
  • Snf1 can phosphorylate recombinant Gcn5 in vitro [29].
  • Here, we show that the C terminus of SSN6 is phosphorylated in vivo and that the SNF1 kinase is not responsible for most of the phosphorylation [30].

Regulatory relationships of SNF1

  • The derepression defect of CAT8 in a cat1 mutant could be suppressed by a mutant Mig1p repressor protein [31].
  • Expression of CAT8 is carbon source regulated and requires a functional Cat1p (Snf1p) protein kinase [31].
  • In two-hybrid assays, one SNF4 mutation enhances the interaction between Snf4 and Snf1 [32].
  • The derepression deficiency of a CSRE-dependent reporter gene in a strain lacking the Cat1 (Snf1) protein kinase can be suppressed by Sip4 fused to a strong heterologous activation domain [33].
  • Characterization of tobacco protein kinase NPK5, a homolog of Saccharomyces cerevisiae SNF1 that constitutively activates expression of the glucose-repressible SUC2 gene for a secreted invertase of S. cerevisiae [6].

Other interactions of SNF1

  • Glucose derepression of gluconeogenesis depends on the active Cat1 (Snf1) protein kinase and the Cat8 zinc cluster activator [34].
  • To identify components of the SNF1 pathway, we isolated multicopy suppressors of defects caused by loss of SNF4, an activator of the SNF1 kinase [22].
  • Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae [16].
  • Previous experimental evidence had indicated that Reg1 might target Glc7 to nuclear substrates such as the Snf1 kinase complex [35].
  • The REG2 gene of Saccharomyces cerevisiae encodes a type 1 protein phosphatase-binding protein that functions with Reg1p and the Snf1 protein kinase to regulate growth [26].
  • These data indicate that Snf1 functions upstream of Gcn20 to regulate control of GCN4 translation in S. cerevisiae [36].

Analytical, diagnostic and therapeutic context of SNF1


  1. Adenosine kinase is inactivated by geminivirus AL2 and L2 proteins. Wang, H., Hao, L., Shung, C.Y., Sunter, G., Bisaro, D.M. Plant Cell (2003) [Pubmed]
  2. SNF1/AMPK/SnRK1 kinases, global regulators at the heart of energy control? Polge, C., Thomas, M. Trends Plant Sci. (2007) [Pubmed]
  3. Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. Thompson-Jaeger, S., François, J., Gaughran, J.P., Tatchell, K. Genetics (1991) [Pubmed]
  4. The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Hardie, D.G., Carling, D., Carlson, M. Annu. Rev. Biochem. (1998) [Pubmed]
  5. Snf1--a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription. Lo, W.S., Duggan, L., Emre, N.C., Belotserkovskya, R., Lane, W.S., Shiekhattar, R., Berger, S.L. Science (2001) [Pubmed]
  6. Characterization of tobacco protein kinase NPK5, a homolog of Saccharomyces cerevisiae SNF1 that constitutively activates expression of the glucose-repressible SUC2 gene for a secreted invertase of S. cerevisiae. Muranaka, T., Banno, H., Machida, Y. Mol. Cell. Biol. (1994) [Pubmed]
  7. Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Wang, Z., Wilson, W.A., Fujino, M.A., Roach, P.J. Mol. Cell. Biol. (2001) [Pubmed]
  8. Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Sutherland, C.M., Hawley, S.A., McCartney, R.R., Leech, A., Stark, M.J., Schmidt, M.C., Hardie, D.G. Curr. Biol. (2003) [Pubmed]
  9. Depression of Saccharomyces cerevisiae invasive growth on non-glucose carbon sources requires the Snf1 kinase. Palecek, S.P., Parikh, A.S., Huh, J.H., Kron, S.J. Mol. Microbiol. (2002) [Pubmed]
  10. Arabidopsis thaliana proteins related to the yeast SIP and SNF4 interact with AKINalpha1, an SNF1-like protein kinase. Bouly, J.P., Gissot, L., Lessard, P., Kreis, M., Thomas, M. Plant J. (1999) [Pubmed]
  11. Control of peroxisome proliferation in Saccharomyces cerevisiae by ADR1, SNF1 (CAT1, CCR1) and SNF4 (CAT3). Simon, M., Binder, M., Adam, G., Hartig, A., Ruis, H. Yeast (1992) [Pubmed]
  12. Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression. da Silva Xavier, G., Leclerc, I., Salt, I.P., Doiron, B., Hardie, D.G., Kahn, A., Rutter, G.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  13. Insulin signaling in the yeast Saccharomyces cerevisiae. 2. Interaction of human insulin with a putative binding protein. Müller, G., Rouveyre, N., Upshon, C., Grobeta, E., Bandlow, W. Biochemistry (1998) [Pubmed]
  14. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate insulin release. Salt, I.P., Johnson, G., Ashcroft, S.J., Hardie, D.G. Biochem. J. (1998) [Pubmed]
  15. Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast. Kuchin, S., Yeghiayan, P., Carlson, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  16. Pho85p, a cyclin-dependent protein kinase, and the Snf1p protein kinase act antagonistically to control glycogen accumulation in Saccharomyces cerevisiae. Huang, D., Farkas, I., Roach, P.J. Mol. Cell. Biol. (1996) [Pubmed]
  17. Expression and regulation of the AMP-activated protein kinase-SNF1 (sucrose non-fermenting 1) kinase complexes in yeast and mammalian cells: studies using chimaeric catalytic subunits. Daniel, T., Carling, D. Biochem. J. (2002) [Pubmed]
  18. Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase. Stapleton, D., Gao, G., Michell, B.J., Widmer, J., Mitchelhill, K., Teh, T., House, C.M., Witters, L.A., Kemp, B.E. J. Biol. Chem. (1994) [Pubmed]
  19. Purification and characterization of Snf1 kinase complexes containing a defined Beta subunit composition. Nath, N., McCartney, R.R., Schmidt, M.C. J. Biol. Chem. (2002) [Pubmed]
  20. Access denied: Snf1 activation loop phosphorylation is controlled by availability of the phosphorylated threonine 210 to the PP1 phosphatase. Rubenstein, E.M., McCartney, R.R., Zhang, C., Shokat, K.M., Shirra, M.K., Arndt, K.M., Schmidt, M.C. J. Biol. Chem. (2008) [Pubmed]
  21. Roles of the glycogen-binding domain and Snf4 in glucose inhibition of SNF1 protein kinase. Momcilovic, M., Iram, S.H., Liu, Y., Carlson, M. J. Biol. Chem. (2008) [Pubmed]
  22. Dosage-dependent modulation of glucose repression by MSN3 (STD1) in Saccharomyces cerevisiae. Hubbard, E.J., Jiang, R., Carlson, M. Mol. Cell. Biol. (1994) [Pubmed]
  23. Regulation of yeast COX6 by the general transcription factor ABF1 and separate HAP2- and heme-responsive elements. Trawick, J.D., Kraut, N., Simon, F.R., Poyton, R.O. Mol. Cell. Biol. (1992) [Pubmed]
  24. Gts1p activates SNF1-dependent derepression of HSP104 and TPS1 in the stationary phase of yeast growth. Yaguchi, S., Tsurugi, K. J. Biol. Chem. (2003) [Pubmed]
  25. Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae. Schüller, H.J. Curr. Genet. (2003) [Pubmed]
  26. The REG2 gene of Saccharomyces cerevisiae encodes a type 1 protein phosphatase-binding protein that functions with Reg1p and the Snf1 protein kinase to regulate growth. Frederick, D.L., Tatchell, K. Mol. Cell. Biol. (1996) [Pubmed]
  27. Snf1 protein kinase regulates phosphorylation of the Mig1 repressor in Saccharomyces cerevisiae. Treitel, M.A., Kuchin, S., Carlson, M. Mol. Cell. Biol. (1998) [Pubmed]
  28. The Snf1 kinase of the filamentous fungus Hypocrea jecorina phosphorylates regulation-relevant serine residues in the yeast carbon catabolite repressor Mig1 but not in the filamentous fungal counterpart Cre1. Cziferszky, A., Seiboth, B., Kubicek, C.P. Fungal Genet. Biol. (2003) [Pubmed]
  29. Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins rescues a gcn5- mutant in HIS3 expression. Liu, Y., Xu, X., Singh-Rodriguez, S., Zhao, Y., Kuo, M.H. Mol. Cell. Biol. (2005) [Pubmed]
  30. The N-terminal TPR region is the functional domain of SSN6, a nuclear phosphoprotein of Saccharomyces cerevisiae. Schultz, J., Marshall-Carlson, L., Carlson, M. Mol. Cell. Biol. (1990) [Pubmed]
  31. Dual influence of the yeast Cat1p (Snf1p) protein kinase on carbon source-dependent transcriptional activation of gluconeogenic genes by the regulatory gene CAT8. Rahner, A., Schöler, A., Martens, E., Gollwitzer, B., Schüller, H.J. Nucleic Acids Res. (1996) [Pubmed]
  32. Evidence for the involvement of the Glc7-Reg1 phosphatase and the Snf1-Snf4 kinase in the regulation of INO1 transcription in Saccharomyces cerevisiae. Shirra, M.K., Arndt, K.M. Genetics (1999) [Pubmed]
  33. Contribution of Cat8 and Sip4 to the transcriptional activation of yeast gluconeogenic genes by carbon source-responsive elements. Hiesinger, M., Roth, S., Meissner, E., Schüller, H.J. Curr. Genet. (2001) [Pubmed]
  34. CAT5, a new gene necessary for derepression of gluconeogenic enzymes in Saccharomyces cerevisiae. Proft, M., Kötter, P., Hedges, D., Bojunga, N., Entian, K.D. EMBO J. (1995) [Pubmed]
  35. Functional analysis of the yeast Glc7-binding protein Reg1 identifies a protein phosphatase type 1-binding motif as essential for repression of ADH2 expression. Dombek, K.M., Voronkova, V., Raney, A., Young, E.T. Mol. Cell. Biol. (1999) [Pubmed]
  36. A chemical genomics study identifies Snf1 as a repressor of GCN4 translation. Shirra, M.K., McCartney, R.R., Zhang, C., Shokat, K.M., Schmidt, M.C., Arndt, K.M. J. Biol. Chem. (2008) [Pubmed]
  37. Mutations in the gal83 glycogen-binding domain activate the snf1/gal83 kinase pathway by a glycogen-independent mechanism. Wiatrowski, H.A., Van Denderen, B.J., Berkey, C.D., Kemp, B.E., Stapleton, D., Carlson, M. Mol. Cell. Biol. (2004) [Pubmed]
  38. Std1p (Msn3p) positively regulates the Snf1 kinase in Saccharomyces cerevisiae. Kuchin, S., Vyas, V.K., Kanter, E., Hong, S.P., Carlson, M. Genetics (2003) [Pubmed]
  39. N-terminal mutations modulate yeast SNF1 protein kinase function. Estruch, F., Treitel, M.A., Yang, X., Carlson, M. Genetics (1992) [Pubmed]
  40. Enhanced gluconeogenesis and increased energy storage as hallmarks of aging in Saccharomyces cerevisiae. Lin, S.S., Manchester, J.K., Gordon, J.I. J. Biol. Chem. (2001) [Pubmed]
  41. Glucose deprivation mediates interaction between CTDK-I and Snf1 in Saccharomyces cerevisiae. Van Driessche, B., Coddens, S., Van Mullem, V., Vandenhaute, J. FEBS Lett. (2005) [Pubmed]
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