HXK2/YGL253W Summary Help

Standard Name HXK2 1
Systematic Name YGL253W
Alias HEX1 , HKB , SCI2
Feature Type ORF, Verified
Description Hexokinase isoenzyme 2; catalyzes phosphorylation of glucose in the cytosol; predominant hexokinase during growth on glucose; functions in the nucleus to repress expression of HXK1 and GLK1 and to induce expression of its own gene; antiapoptotic; phosphorylation/dephosphorylation at serine-14 by protein kinase Snf1p and protein phosphatase Glc7p-Reg1p regulates nucleocytoplasmic shuttling of Hxk2p; HXK2 has a paralog, HXK1, that arose from the whole genome duplication (2, 3, 4, 5, 6 and see Summary Paragraph)
Name Description HeXoKinase
Chromosomal Location
ChrVII:23935 to 25395 | ORF Map | GBrowse
Genetic position: -167 cM
Gene Ontology Annotations All HXK2 GO evidence and references
  View Computational GO annotations for HXK2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 9 genes
Classical genetics
reduction of function
Large-scale survey
243 total interaction(s) for 150 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 15
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 12
  • Biochemical Activity: 1
  • Co-localization: 1
  • Reconstituted Complex: 6
  • Two-hybrid: 6

Genetic Interactions
  • Negative Genetic: 112
  • Phenotypic Enhancement: 24
  • Phenotypic Suppression: 5
  • Positive Genetic: 40
  • Synthetic Growth Defect: 8
  • Synthetic Lethality: 5
  • Synthetic Rescue: 4

Expression Summary
Length (a.a.) 486
Molecular Weight (Da) 53,942
Isoelectric Point (pI) 5.02
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVII:23935 to 25395 | ORF Map | GBrowse
Genetic position: -167 cM
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1461 23935..25395 1996-07-31 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000003222

The first irreversible step in the intracellular metabolism of glucose involves the phosphorylation of glucose at C6. In Saccharomyces cerevisiae, this can be catalysed by three enzymes, namely the hexokinases Hxk1p and Hxk2p and the glucokinase Glk1p (7, 8, 3). All three proteins are involved in the uptake of glucose (9), however Hxk2p appears to play the main role during glucose phosphorylation in vivo, because it is the predominant isoenzyme during growth on glucose (7, 3). The HXK2 gene is expressed when yeast cells are grown on a fermentable medium using glucose, fructose or mannose as a carbon source (9, 10). When cells are shifted to a non-fermentable carbon source, the HXK2 gene is repressed and the HXK1 and GLK1 genes are rapidly de-repressed (11, 2).

Hxk2p is predominantly found in the cytosol where it is a key enzyme in glycolysis. However, Hxk2p is also found in the nucleus where it is required for the glucose-induced repression of several genes, including HXK1 and GLK1, and for glucose-induced expression of its own gene, HXK2 (2, 12, 13, 14). Interestingly, Hxk2p also plays a role in replicative cell aging because deletion of HXK2 significantly enhances yeast longevity (15).

HXK1, HXK2, and GLK1 homologs have been identified in fission yeast, rice, arabidopsis, and mammals (16, 17, 18). In pancreatic cells, human glucokinase/hexokinase IV (GCK/HK4; OMIM), a functional homolog of S. cerevisiae genes HXK1, HXK2, and GLK1, acts as a glucose sensor and is involved in regulating insulin secretion. Mutations in GCK/HK4 have been associated with the diseases, familial hyperinsulinemic hypoglycemia-3 (OMIM) and the form of late-onset noninsulin-dependent diabetes mellitus known as type II maturity-onset diabetes of the young (OMIM) (19).

Last updated: 2006-11-29 Contact SGD

References cited on this page View Complete Literature Guide for HXK2
1) Link, A. and Olson, M.  (1989) Personal Communication, Mortimer Map Edition 10
2) Rodriguez A, et al.  (2001) The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2 genes of Saccharomyces cerevisiae. Biochem J 355(Pt 3):625-31
3) Bianconi ML  (2003) Calorimetric determination of thermodynamic parameters of reaction reveals different enthalpic compensations of the yeast hexokinase isozymes. J Biol Chem 278(21):18709-13
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Fernandez-Garcia P, et al.  (2012) Phosphorylation of yeast hexokinase 2 regulates its nucleocytoplasmic shuttling. J Biol Chem 287(50):42151-64
6) Amigoni L, et al.  (2013) Lack of Induces Localization of Active Ras in Mitochondria and Triggers Apoptosis in the Yeast Oxid Med Cell Longev 2013():678473
7) Walsh RB, et al.  (1983) Cloning of genes that complement yeast hexokinase and glucokinase mutants. J Bacteriol 154(2):1002-4
8) Clifton D, et al.  (1993) Functional studies of yeast glucokinase. J Bacteriol 175(11):3289-94
9) Bisson LF and Fraenkel DG  (1983) Involvement of kinases in glucose and fructose uptake by Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 80(6):1730-4
10) De Winde JH, et al.  (1996) Differential requirement of the yeast sugar kinases for sugar sensing in establishing the catabolite-repressed state. Eur J Biochem 241(2):633-43
11) Lobo Z and Maitra PK  (1977) Physiological role of glucose-phosphorylating enzymes in Saccharomyces cerevisiae. Arch Biochem Biophys 182(2):639-45
12) Gancedo JM  (1998) Yeast carbon catabolite repression. Microbiol Mol Biol Rev 62(2):334-61
13) Johnston M  (1999) Feasting, fasting and fermenting. Glucose sensing in yeast and other cells. Trends Genet 15(1):29-33
14) Randez-Gil F, et al.  (1998) Hexokinase PII has a double cytosolic-nuclear localisation in Saccharomyces cerevisiae. FEBS Lett 425(3):475-8
15) Kaeberlein M, et al.  (2005) Genes determining yeast replicative life span in a long-lived genetic background. Mech Ageing Dev 126(4):491-504
16) Petit T, et al.  (1996) Schizosaccharomyces pombe possesses an unusual and a conventional hexokinase: biochemical and molecular characterization of both hexokinases. FEBS Lett 378(2):185-9
17) Cho JI, et al.  (2006) Structure, expression, and functional analysis of the hexokinase gene family in rice (Oryza sativa L.). Planta 224(3):598-611
18) Miller S, et al.  (2007) Kinetic and proteomic analyses of S-nitrosoglutathione-treated hexokinase A: consequences for cancer energy metabolism. Amino Acids 32(4):593-602
19) Mayordomo I and Sanz P  (2001) Human pancreatic glucokinase (GlkB) complements the glucose signalling defect of Saccharomyces cerevisiae hxk2 mutants. Yeast 18(14):1309-16