Gene Symbol: HXK2
Description: hexokinase 2
Alias: HEX1, HKB, SCI2, hexokinase 2
Species: Saccharomyces cerevisiae S288c
Products:     HXK2

Top Publications

  1. de la Cera T, Herrero P, Moreno Herrero F, Chaves R, Moreno F. Mediator factor Med8p interacts with the hexokinase 2: implication in the glucose signalling pathway of Saccharomyces cerevisiae. J Mol Biol. 2002;319:703-14 pubmed
    In the presence of glucose the protein hexokinase 2 (Hxk2p), normally resident in the cytosol, is translocated to the nucleus where it impairs the activation of transcription of the glucose-repressed genes HXK1, GLK1 and SUC2, and ..
  2. Schuurmans J, Rossell S, van Tuijl A, Bakker B, Hellingwerf K, Teixeira de Mattos M. Effect of hxk2 deletion and HAP4 overexpression on fermentative capacity in Saccharomyces cerevisiae. FEMS Yeast Res. 2008;8:195-203 pubmed publisher
    ..Whereas overproduction of Hap4p behaved similar to the wild-type strain, deletion of hxk2 resulted in a very different FC profile...
  3. Ahuatzi D, Riera A, Pelaez R, Herrero P, Moreno F. Hxk2 regulates the phosphorylation state of Mig1 and therefore its nucleocytoplasmic distribution. J Biol Chem. 2007;282:4485-93 pubmed
    Mig1 and Hxk2 are two major mediators of glucose repression in Saccharomyces cerevisiae. However, the mechanism by which Hxk2 participates in the glucose repression signaling pathway is not completely understood...
  4. Pelaez R, Herrero P, Moreno F. Nuclear export of the yeast hexokinase 2 protein requires the Xpo1 (Crm1)-dependent pathway. J Biol Chem. 2009;284:20548-55 pubmed publisher
    b>Hexokinase 2 (Hxk2) from Saccharomyces cerevisiae was one of the first metabolic enzymes described as a multifunctional protein...
  5. Rodriguez A, de la Cera T, Herrero P, Moreno F. The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2 genes of Saccharomyces cerevisiae. Biochem J. 2001;355:625-31 pubmed
    The key glycolytic HXK2 gene, coding for the enzyme hexokinase 2 (Hxk2p), is expressed when cells of the yeast Saccharomyces cerevisiae are grown on a fermentable medium using glucose, fructose or mannose as a carbon source...
  6. Hohmann S, Winderickx J, de Winde J, Valckx D, Cobbaert P, Luyten K, et al. Novel alleles of yeast hexokinase PII with distinct effects on catalytic activity and catabolite repression of SUC2. Microbiology. 1999;145 ( Pt 3):703-14 pubmed
    ..The phosphorylation of glucose or fructose is catalysed by hexokinase PI (Hxk1), hexokinase PII (Hxk2) and a specific glucokinase (Glk1)...
  7. Ma H, Botstein D. Effects of null mutations in the hexokinase genes of Saccharomyces cerevisiae on catabolite repression. Mol Cell Biol. 1986;6:4046-52 pubmed
    ..We constructed null mutations in both hexokinase genes, HXK1 and HXK2, and studied their effect on the fermentation of fructose and on catabolite repression of three different genes in ..
  8. Belinchon M, Gancedo J. Different signalling pathways mediate glucose induction of SUC2, HXT1 and pyruvate decarboxylase in yeast. FEMS Yeast Res. 2007;7:40-7 pubmed
    ..The induction of HXT1 was not affected by the absence of Gpr1. In an hxk1 hxk2 glk1 strain, high glucose fully induced SUC2, caused partial induction of HXT1 and had no effect on Pdc...
  9. Palomino A, Herrero P, Moreno F. Tpk3 and Snf1 protein kinases regulate Rgt1 association with Saccharomyces cerevisiae HXK2 promoter. Nucleic Acids Res. 2006;34:1427-38 pubmed
    b>Hexokinase 2 is an essential factor for signalling repression through the Saccharomyces cerevisiae high-glucose sensing pathway...

More Information


  1. Kaeberlein M, Kirkland K, Fields S, Kennedy B. Genes determining yeast replicative life span in a long-lived genetic background. Mech Ageing Dev. 2005;126:491-504 pubmed
    ..to increase yeast life span, we find that deletion of FOB1, deletion of SCH9, and deletion of GPA2, GPR1, or HXK2 (three genetic models of calorie restriction) significantly enhanced longevity...
  2. Palomino A, Herrero P, Moreno F. Rgt1, a glucose sensing transcription factor, is required for transcriptional repression of the HXK2 gene in Saccharomyces cerevisiae. Biochem J. 2005;388:697-703 pubmed
    Expression of HXK2, a gene encoding a Saccharomyces cerevisiae bifunctional protein with catalytic and regulatory functions, is controlled by glucose availability, being activated in the presence of glucose and inhibited when the levels ..
  3. Ahuatzi D, Herrero P, de la Cera T, Moreno F. The glucose-regulated nuclear localization of hexokinase 2 in Saccharomyces cerevisiae is Mig1-dependent. J Biol Chem. 2004;279:14440-6 pubmed
    Two major mediators of glucose repression in Saccharomyces cerevisiae are the proteins Mig1 and Hxk2. The mechanism of Hxk2-dependent glucose repression pathway is not well understood, but the Mig1-dependent part of the pathway has been ..
  4. Randez Gil F, Herrero P, Sanz P, Prieto J, Moreno F. Hexokinase PII has a double cytosolic-nuclear localisation in Saccharomyces cerevisiae. FEBS Lett. 1998;425:475-8 pubmed
    We describe here that the HXK2 gene product, isoenzyme PII of hexokinase, is located in both the nucleus and the cytoplasm of Saccharomyces cerevisiae cells...
  5. Kaeberlein M, Kirkland K, Fields S, Kennedy B. Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol. 2004;2:E296 pubmed
    ..These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes. ..
  6. Würtz C, Schliebs W, Erdmann R, Rottensteiner H. Dynamin-like protein-dependent formation of Woronin bodies in Saccharomyces cerevisiae upon heterologous expression of a single protein. FEBS J. 2008;275:2932-41 pubmed publisher
    ..The dominant protein of the Neurospora crassa Woronin body, HEX1, forms a hexagonal core crystal via oligomerization and evidence has accumulated that Woronin bodies bud off from ..
  7. Brandina I, Graham J, Lemaitre Guillier C, Entelis N, Krasheninnikov I, Sweetlove L, et al. Enolase takes part in a macromolecular complex associated to mitochondria in yeast. Biochim Biophys Acta. 2006;1757:1217-28 pubmed
    ..This suggests an unsuspected novel function for this complex in tRNA mitochondrial import. ..
  8. Kang H, Kang W, Go S, Rezaee A, Krishna S, Rhee S, et al. Characteristics of Saccharomyces cerevisiae gal1 Delta and gal1 Delta hxk2 Delta mutants expressing recombinant proteins from the GAL promoter. Biotechnol Bioeng. 2005;89:619-29 pubmed
    ..of the gal1 Delta mutant strain as a host for heterologous protein production, a null mutation of either MIG1 or HXK2 was introduced into the gal1 Delta mutant strain, generating gal1 Delta mig1 Delta and gal1 Delta hxk2 Delta double ..
  9. Hung G, Brown C, Wolfe A, Liu J, Chiang H. Degradation of the gluconeogenic enzymes fructose-1,6-bisphosphatase and malate dehydrogenase is mediated by distinct proteolytic pathways and signaling events. J Biol Chem. 2004;279:49138-50 pubmed
    ..By contrast, the cAMP-dependent signaling pathway was not involved in the non-vacuolar degradation of these proteins, although the phosphorylation of glucose was required. ..
  10. Pelaez R, Herrero P, Moreno F. Functional domains of yeast hexokinase 2. Biochem J. 2010;432:181-90 pubmed publisher
    Hkx2 (hexokinase 2) from Saccharomyces cerevisiae was one of the first metabolic enzymes described as a multifunctional protein...
  11. Pelaez R, Fernández García P, Herrero P, Moreno F. Nuclear import of the yeast hexokinase 2 protein requires ?/?-importin-dependent pathway. J Biol Chem. 2012;287:3518-29 pubmed publisher
    b>Hexokinase 2 (Hxk2) from Saccharomyces cerevisiae was one of the first metabolic enzymes described as a multifunctional protein...
  12. Kaps S, Kettner K, Migotti R, Kanashova T, Krause U, Rödel G, et al. Protein kinase Ymr291w/Tda1 is essential for glucose signaling in saccharomyces cerevisiae on the level of hexokinase isoenzyme ScHxk2 phosphorylation*. J Biol Chem. 2015;290:6243-55 pubmed publisher
    ..cerevisiae and the homologous KLLA0A09713 gene of Kluyveromyces lactis allow for cross-complementation of the respective protein kinase single-gene deletion strains. ..
  13. Walsh R, Kawasaki G, Fraenkel D. Cloning of genes that complement yeast hexokinase and glucokinase mutants. J Bacteriol. 1983;154:1002-4 pubmed
    Genes complementing the glucose-negative fructose-negative Saccharomyces cerevisiae triple mutant strain (hxkl hxk2 glk1), which lacks hexokinase PI, hexokinase PII, and glucokinase, were obtained from a pool of yeast DNA in the multicopy ..
  14. Yao Y, Tsuchiyama S, Yang C, Bulteau A, He C, Robison B, et al. Proteasomes, Sir2, and Hxk2 form an interconnected aging network that impinges on the AMPK/Snf1-regulated transcriptional repressor Mig1. PLoS Genet. 2015;11:e1004968 pubmed publisher
    ..in two other long-lived yeast aging models: cells that overexpress SIR2 or deleted for the Mig1-regulator HXK2. Finally, compromised proteasome function blocks lifespan extension in both strains...
  15. Skowronek E, Grzechnik P, Späth B, Marchfelder A, Kufel J. tRNA 3' processing in yeast involves tRNase Z, Rex1, and Rrp6. RNA. 2014;20:115-30 pubmed publisher
    ..In addition to its function in the nucleus, Trz1 processes the 3' ends of mitochondrial tRNAs, contributing to the general RNA metabolism in this organelle. ..
  16. McCartney R, Chandrashekarappa D, Zhang B, Schmidt M. Genetic analysis of resistance and sensitivity to 2-deoxyglucose in Saccharomyces cerevisiae. Genetics. 2014;198:635-46 pubmed publisher
    ..Snf1 kinase activated by 2-deoxyglucose does not phosphorylate the Mig1 protein, a known Snf1 substrate during glucose limitation. Thus, different stimuli elicit distinct responses from the Snf1 kinase. ..
  17. Lobo Z, Maitra P. Genetics of yeast hexokinase. Genetics. 1977;86:727-44 pubmed
    ..Both mutant strains grow on glucose but are unable to grow on fructose, and contain two mutant genes hxk1 and hxk2 each. The mutations are recessive and noncomplementing...
  18. Vega M, Riera A, Fernández Cid A, Herrero P, Moreno F. Hexokinase 2 Is an Intracellular Glucose Sensor of Yeast Cells That Maintains the Structure and Activity of Mig1 Protein Repressor Complex. J Biol Chem. 2016;291:7267-85 pubmed publisher
    b>Hexokinase 2 (Hxk2) fromSaccharomyces cerevisiaeis a bi-functional enzyme, being both a catalyst in the cytosol and an important regulator of the glucose repression signal in the nucleus...
  19. Kettner K, Krause U, Mosler S, Bodenstein C, Kriegel T, Rödel G. Saccharomyces cerevisiae gene YMR291W/TDA1 mediates the in vivo phosphorylation of hexokinase isoenzyme 2 at serine-15. FEBS Lett. 2012;586:455-8 pubmed publisher
    b>Hxk2 is the predominant hexokinase of Saccharomyces cerevisiae during growth on glucose. In addition to its role in glycolysis, the enzyme is involved in glucose sensing and regulation of gene expression...
  20. Lobo Z, Maitra P. Physiological role of glucose-phosphorylating enzymes in Saccharomyces cerevisiae. Arch Biochem Biophys. 1977;182:639-45 pubmed
  21. Konarzewska P, Sherr G, Ahmed S, Ursomanno B, Shen C. Vma3p protects cells from programmed cell death through the regulation of Hxk2p expression. Biochem Biophys Res Commun. 2017;493:233-239 pubmed publisher
    ..HXK2 encodes hexokinase 2 which can phosphorylate glucose during phospholipid biosynthesis...
  22. Amigoni L, Frigerio G, Martegani E, Colombo S. Involvement of Aif1 in apoptosis triggered by lack of Hxk2 in the yeast Saccharomyces cerevisiae. FEMS Yeast Res. 2016;16: pubmed publisher
    ..an increase of both apoptotic and necrotic cells compared with the wild-type strain, providing a new role for hexokinase 2 (EC 2.7.1...
  23. de Winde J, Crauwels M, Hohmann S, Thevelein J, Winderickx J. Differential requirement of the yeast sugar kinases for sugar sensing in establishing the catabolite-repressed state. Eur J Biochem. 1996;241:633-43 pubmed
    ..We have investigated transcriptional regulation of the SUC2 gene encoding repressible invertase, and of HXK1, HXK2 and GLK1 encoding the three known yeast hexose kinases during transition from derepressed to repressed growth ..
  24. Hu Z, Yue Y, Jiang H, Zhang B, Sherwood P, Michels C. Analysis of the mechanism by which glucose inhibits maltose induction of MAL gene expression in Saccharomyces. Genetics. 2000;154:121-32 pubmed
    ..The glucose inhibition pathway requires HXK2, REG1, and GSF1 and appears to overlap upstream with the glucose repression pathway...
  25. De Silva Udawatta M, Cannon J. Roles of trehalose phosphate synthase in yeast glycogen metabolism and sporulation. Mol Microbiol. 2001;40:1345-56 pubmed
    ..Furthermore, high-copy MCK1 or heterozygous hxk2 mutations can suppress the tps1 sporulation trait...
  26. Noubhani A, Bunoust O, Bonini B, Thevelein J, Devin A, Rigoulet M. The trehalose pathway regulates mitochondrial respiratory chain content through hexokinase 2 and cAMP in Saccharomyces cerevisiae. J Biol Chem. 2009;284:27229-34 pubmed publisher
    ..This is the first time that a pathway involved in sugar storage, i.e. trehalose, is shown to regulate the mitochondrial enzymatic content. ..
  27. Jiang H, Medintz I, Zhang B, Michels C. Metabolic signals trigger glucose-induced inactivation of maltose permease in Saccharomyces. J Bacteriol. 2000;182:647-54 pubmed
    ..We find that pathway 2 is dependent on HXK2 and to a lesser extent HXK1...
  28. Karhumaa K, Wu B, Kielland Brandt M. Conditions with high intracellular glucose inhibit sensing through glucose sensor Snf3 in Saccharomyces cerevisiae. J Cell Biochem. 2010;110:920-5 pubmed publisher
    ..The apparent affinity for glucose was lowest when the intracellular glucose concentration was high. The results conform to an alternating-access model for transporter-like sensors. ..
  29. Bisson L, Fraenkel D. Involvement of kinases in glucose and fructose uptake by Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1983;80:1730-4 pubmed
    ..analog 6-deoxyglucose was measured in wild-type Saccharomyces cerevisiae and two mutant strains, one (hxk1 hxk2) lacking both hexokinase A(P-I) and B(P-II) but containing glucokinase (and hence able to grow on glucose but not ..
  30. Fernández García P, Pelaez R, Herrero P, Moreno F. Phosphorylation of yeast hexokinase 2 regulates its nucleocytoplasmic shuttling. J Biol Chem. 2012;287:42151-64 pubmed publisher
    Nucleocytoplasmic shuttling of Hxk2 induced by glucose levels has been reported recently. Here we present evidence that indicates that Hxk2 nucleocytoplasmic traffic is regulated by phosphorylation and dephosphorylation at serine 14...
  31. Reddi A, Culotta V. SOD1 integrates signals from oxygen and glucose to repress respiration. Cell. 2013;152:224-35 pubmed publisher
    ..Our data therefore may provide mechanistic insight into how rapidly proliferating cells and many cancers accomplish glucose-mediated repression of respiration in favor of aerobic glycolysis. ..
  32. Randez Gil F, Sanz P, Entian K, Prieto J. Carbon source-dependent phosphorylation of hexokinase PII and its role in the glucose-signaling response in yeast. Mol Cell Biol. 1998;18:2940-8 pubmed
    The HXK2 gene is required for a variety of regulatory effects leading to an adaptation for fermentative metabolism in Saccharomyces cerevisiae. However, the molecular basis of the specific role of Hxk2p in these effects is still unclear...
  33. Bianconi M. Calorimetric determination of thermodynamic parameters of reaction reveals different enthalpic compensations of the yeast hexokinase isozymes. J Biol Chem. 2003;278:18709-13 pubmed
    The change in enthalpy and rate constants for the reactions of yeast hexokinase isozymes, PI (Hxk1) and PII (Hxk2), was determined at pH 7.6 and 25 degrees C by isothermal titration calorimetry...
  34. Hohmann S, Neves M, de Koning W, Alijo R, Ramos J, Thevelein J. The growth and signalling defects of the ggs1 (fdp1/byp1) deletion mutant on glucose are suppressed by a deletion of the gene encoding hexokinase PII. Curr Genet. 1993;23:281-9 pubmed
    ..We reduced hexokinase activity in ggs1 strains by deleting the gene HXK2 encoding hexokinase PII. The double mutant ggs1 delta, hxk2 delta grew on glucose...
  35. Ramshini H, Rezaei Ghaleh N, Ebrahim Habibi A, Saboury A, Nemat Gorgani M. Thermally induced changes in the structure and activity of yeast hexokinase B. Biophys Chem. 2008;137:88-94 pubmed publisher
    ..Deamidation of a critical Asn or Gln residue(s) may also play an important role. ..
  36. Barbosa A, Pereira C, Osorio H, Moradas Ferreira P, Costa V. The ceramide-activated protein phosphatase Sit4p controls lifespan, mitochondrial function and cell cycle progression by regulating hexokinase 2 phosphorylation. Cell Cycle. 2016;15:1620-30 pubmed publisher
    ..In this study, we show that hexokinase 2 (Hxk2p) is hyperphosphorylated in sit4? mutants grown in glucose medium by a Snf1p-independent mechanism and ..
  37. Deroover S, Ghillebert R, Broeckx T, Winderickx J, Rolland F. Trehalose-6-phosphate synthesis controls yeast gluconeogenesis downstream and independent of SNF1. FEMS Yeast Res. 2016;16: pubmed publisher
    ..While SNF1 is essential for induction of gluconeogenesis, T6P/TPS is required for inactivation of gluconeogenesis in the presence of glucose, downstream and independent of SNF1 activity and the Cat8 and Sip4 transcription factors. ..
  38. Searle J, Wood M, Kaur M, Tobin D, Sanchez Y. Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage. PLoS Genet. 2011;7:e1002176 pubmed publisher
    ..Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA. ..
  39. Belinchon M, Gancedo J. Glucose controls multiple processes in Saccharomyces cerevisiae through diverse combinations of signaling pathways. FEMS Yeast Res. 2007;7:808-18 pubmed
    We have studied how the lack of glucose sensors in the plasma membrane, or of the enzymes Hxk1, Hxk2, Glk1, which catalyze the first intracellular step in glucose metabolism, affect the different responses of Saccharomyces cerevisiae to ..