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Gene Review

GLK1  -  glucokinase

Saccharomyces cerevisiae S288c

Synonyms: GLK-1, Glucokinase-1, Glucose kinase 1, HOR3, YCL040W, ...
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Disease relevance of GLK1

  • The highest titers and yields of shikimic acid biosynthesized from glucose in 1 L fermentor runs were achieved using E. coli SP1.lpts/pSC6.090B, which expressed both Z. mobilis glf-encoded glucose facilitator protein and Z. mobilis glk-encoded glucose kinase in a host deficient in the phosphoenolpyruvate:carbohydrate phosphotransferase system [1].

High impact information on GLK1

  • This repression remains operative in yeast mutants carrying any one of the three hexose kinases, but is lost in a triple hxk1, hxk2, glk1 mutant [2].
  • We have also demonstrated the involvement of Hxk1p as a negative factor in the expression of the GLK1 and HXK2 genes [3].
  • Full expression of the GLK1 gene is produced by inductive activation of three STRE when Msn2 and Msn4 proteins are translocated to the nucleus by covalent modification [4].
  • In order to achieve the severe glucose repression of GLK1, constitutive repressor factors acting through the ERA/TAB element must counteract constitutive activation generated by Gcr1 binding to the GCR1 element [4].
  • The combinatorial effect of the entire region leads to the regulated transcription of GLK1, i.e., silent in media with glucose and other preferred carbon sources, such as fructose or mannose, and increased levels of expression upon glucose depletion [4].

Biological context of GLK1


Anatomical context of GLK1

  • These findings reveal a novel mechanism of gene regulation whereby the product of a glycolytic gene, normally resident in the cytosol, interacts directly with nuclear proteins to regulate the transcription of the HXK1 and GLK1 genes and to autoregulate its own transcription [3].
  • The "in vitro" activation by glucose of the RAS-adenylate cyclase system in membranes from a strain of Saccharomyces cerevisiae lacking any functional glucose kinase activity presents similar features to those of the wild type [7].

Associations of GLK1 with chemical compounds

  • Both HXK1 and GLK1 are repressed upon addition of glucose or fructose [8].
  • In both GLK and the hexokinases, a lysine residue is also conserved at aa position 110 which probably corresponds to the ATP-binding site [6].

Other interactions of GLK1

  • Because the in vivo functions of the Hxk1p and Glk1p enzymes have remained a mystery so far, we have investigated this glucose-induced regulatory process [3].
  • An early repression response requires any one of the three glucose kinases present in S. cerevisiae (HXK1, HXK2, or GLK1) [9].
  • YCL312 encodes glucokinase, and YCL313 the protein disulfide isomerase [10].


  1. Phosphoenolpyruvate availability and the biosynthesis of shikimic acid. Chandran, S.S., Yi, J., Draths, K.M., von Daeniken, R., Weber, W., Frost, J.W. Biotechnol. Prog. (2003) [Pubmed]
  2. Multiple signalling pathways trigger the exquisite sensitivity of yeast gluconeogenic mRNAs to glucose. Yin, Z., Smith, R.J., Brown, A.J. Mol. Microbiol. (1996) [Pubmed]
  3. The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2 genes of Saccharomyces cerevisiae. Rodríguez, A., De La Cera, T., Herrero, P., Moreno, F. Biochem. J. (2001) [Pubmed]
  4. Functional characterization of transcriptional regulatory elements in the upstream region of the yeast GLK1 gene. Herrero, P., Flores, L., de la Cera, T., Moreno, F. Biochem. J. (1999) [Pubmed]
  5. Genetics of yeast glucokinase. Maitra, P.K., Lobo, Z. Genetics (1983) [Pubmed]
  6. Structure of yeast glucokinase, a strongly diverged specific aldo-hexose-phosphorylating isoenzyme. Albig, W., Entian, K.D. Gene (1988) [Pubmed]
  7. Glucose activation of adenylate cyclase in Saccharomyces cerevisiae mutants lacking glucose-phosphorylating enzymes. Pardo, L.A., Lazo, P.S., Ramos, S. Cell. Signal. (1993) [Pubmed]
  8. Differential requirement of the yeast sugar kinases for sugar sensing in establishing the catabolite-repressed state. De Winde, J.H., Crauwels, M., Hohmann, S., Thevelein, J.M., Winderickx, J. Eur. J. Biochem. (1996) [Pubmed]
  9. Glucose repression may involve processes with different sugar kinase requirements. Sanz, P., Nieto, A., Prieto, J.A. J. Bacteriol. (1996) [Pubmed]
  10. The complete sequence of a 9,543 bp segment on the left arm of chromosome III reveals five open reading frames including glucokinase and the protein disulfide isomerase. Scherens, B., Messenguy, F., Gigot, D., Dubois, E. Yeast (1992) [Pubmed]
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