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Gene Review

GRR1  -  SCF ubiquitin ligase complex subunit GRR1

Saccharomyces cerevisiae S288c

Synonyms: CAT80, COT2, F-box and leucine-rich repeat protein GRR1, F-box/LRR-repeat protein GRR1, J1885, ...
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High impact information on GRR1

  • GRR1 encodes the yeast F-box protein that is part of the SCF-GRR1 Ubiquitin proteolysis machinery that is required for regulating cell cycle in response to glucose signaling. [1]
  • Surprisingly, one group of mutants was found to be allelic to GRR1, a gene previously described to be involved in glucose uptake, glucose repression, and divalent cation transport [2].
  • This suggests that the GRR1 gene product is part of a common regulatory pathway linking two functions important for cell growth, nutrient uptake, and G1 cyclin-controlled cell division [2].
  • The same mutations resulted in the stabilization of Cln2 and Gic2 and also in a spectrum of phenotypes characteristic of inactivation of GRR1, including hyperpolarization and enhancement of pseudohyphal growth [3].
  • Strains that carry a COT2 allele conferring complete loss of function are viable and exhibit phenotypes similar to those of spontaneous cot2 mutations [4].
  • The glucose dependence of the transport defect implies that cot2 mutations affect the link between glucose metabolism and divalent cation active transport [4].

Biological context of GRR1

  • Principal components analysis of the summed fractional labelling data show that deleting the genes HXK2 and GRR1 results in similar phenotype at the fluxome level, with a partial alleviation of glucose repression on the respiratory metabolism [5].
  • GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions [6].
  • The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression [6].
  • Deletion of GRR1 from the C. albicans genome results in a highly filamentous, pseudohyphal morphology under conditions that normally promote the yeast form of growth [7].
  • The function of either gene product seems to be more important in metal homeostasis than is the GRR1 gene product, which is also involved in metal metabolism [8].

Associations of GRR1 with chemical compounds

  • GRR1 seems to encode a positive regulator of HXT expression, since grr1 mutants are defective in glucose induction of all four HXT genes [9].
  • Overexpression in GRR1 cells resulted in sulfite sensitivity, suggesting a connection between CLN1 and sulfite metabolism [10].
  • Comparison of the grr1Delta strain with the reference strain in the absence of citrulline revealed that GRR1 disruption leads to increased transcription of numerous genes [11].

Other interactions of GRR1

  • GRR1 protein interacts with SKP1 protein. Along with CDC53 protein, they form the yeast SCF-GRR1 ubiquitin conjugating ligase complex [1]
  • RGT2 and GRR1 also play a role in regulating the expression of the HXT genes, which appear to be the upstream components of the glucose-transport-dependent pathway regulating maltose permease inactivation [12].
  • New SNF genes, GAL11 and GRR1 affect SUC2 expression in Saccharomyces cerevisiae [13].
  • These mutations, designated generically elm (elongated morphology), defined 14 genes; two of these corresponded to the previously described genes GRR1 and CDC12 [14].
  • These findings suggest that GRR1 and SNF3 affect glucose transport by distinct pathways [15].
  • Multicopy suppression analysis, undertaken to explore relationships among genes previously implicated in sulfite metabolism, suggests a regulatory pathway in which SSU1 acts downstream of FZF1 and SSU3, which in turn act downstream of GRR1 [16].

Analytical, diagnostic and therapeutic context of GRR1

  • Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts [6].


  1. Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle. Li, F.N., Johnston, M. EMBO. J. (1997) [Pubmed]
  2. G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast. Barral, Y., Jentsch, S., Mann, C. Genes Dev. (1995) [Pubmed]
  3. F-box protein Grr1 interacts with phosphorylated targets via the cationic surface of its leucine-rich repeat. Hsiung, Y.G., Chang, H.C., Pellequer, J.L., La Valle, R., Lanker, S., Wittenberg, C. Mol. Cell. Biol. (2001) [Pubmed]
  4. The COT2 gene is required for glucose-dependent divalent cation transport in Saccharomyces cerevisiae. Conklin, D.S., Kung, C., Culbertson, M.R. Mol. Cell. Biol. (1993) [Pubmed]
  5. Phenotypic characterization of glucose repression mutants of Saccharomyces cerevisiae using experiments with 13C-labelled glucose. Raghevendran, V., Gombert, A.K., Christensen, B., Kötter, P., Nielsen, J. Yeast (2004) [Pubmed]
  6. GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats. Flick, J.S., Johnston, M. Mol. Cell. Biol. (1991) [Pubmed]
  7. The GRR1 gene of Candida albicans is involved in the negative control of pseudohyphal morphogenesis. Butler, D.K., All, O., Goffena, J., Loveless, T., Wilson, T., Toenjes, K.A. Fungal Genet. Biol. (2006) [Pubmed]
  8. Interactions between gene products involved in divalent cation transport in Saccharomyces cerevisiae. Conklin, D.S., Culbertson, M.R., Kung, C. Mol. Gen. Genet. (1994) [Pubmed]
  9. Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. Ozcan, S., Johnston, M. Mol. Cell. Biol. (1995) [Pubmed]
  10. Multicopy FZF1 (SUL1) suppresses the sulfite sensitivity but not the glucose derepression or aberrant cell morphology of a grr1 mutant of Saccharomyces cerevisiae. Avram, D., Bakalinsky, A.T. Genetics (1996) [Pubmed]
  11. Grr1p is required for transcriptional induction of amino acid permease genes and proper transcriptional regulation of genes in carbon metabolism of Saccharomyces cerevisiae. Eckert-Boulet, N., Regenberg, B., Nielsen, J. Curr. Genet. (2005) [Pubmed]
  12. Two glucose sensing/signaling pathways stimulate glucose-induced inactivation of maltose permease in Saccharomyces. Jiang, H., Medintz, I., Michels, C.A. Mol. Biol. Cell (1997) [Pubmed]
  13. New SNF genes, GAL11 and GRR1 affect SUC2 expression in Saccharomyces cerevisiae. Vallier, L.G., Carlson, M. Genetics (1991) [Pubmed]
  14. Mutational analysis of morphologic differentiation in Saccharomyces cerevisiae. Blacketer, M.J., Madaule, P., Myers, A.M. Genetics (1995) [Pubmed]
  15. Altered regulatory responses to glucose are associated with a glucose transport defect in grr1 mutants of Saccharomyces cerevisiae. Vallier, L.G., Coons, D., Bisson, L.F., Carlson, M. Genetics (1994) [Pubmed]
  16. SSU1 encodes a plasma membrane protein with a central role in a network of proteins conferring sulfite tolerance in Saccharomyces cerevisiae. Avram, D., Bakalinsky, A.T. J. Bacteriol. (1997) [Pubmed]
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