GLK1/YCL040W Summary Help

Standard Name GLK1 1
Systematic Name YCL040W
Alias HOR3 2
Feature Type ORF, Verified
Description Glucokinase; catalyzes the phosphorylation of glucose at C6 in the first irreversible step of glucose metabolism; one of three glucose phosphorylating enzymes; expression regulated by non-fermentable carbon sources; GLK1 has a paralog, EMI2, that arose from the whole genome duplication (3, 4, 5 and see Summary Paragraph)
Name Description GLucoKinase 1
Chromosomal Location
ChrIII:50838 to 52340 | ORF Map | GBrowse
Genetic position: -47 cM
Gene Ontology Annotations All GLK1 GO evidence and references
  View Computational GO annotations for GLK1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Regulators 42 genes
Classical genetics
Large-scale survey
40 total interaction(s) for 30 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 12
  • Affinity Capture-RNA: 5
  • Biochemical Activity: 1
  • Co-purification: 1
  • Two-hybrid: 4

Genetic Interactions
  • Negative Genetic: 3
  • Phenotypic Enhancement: 6
  • Positive Genetic: 3
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 4

Expression Summary
Length (a.a.) 500
Molecular Weight (Da) 55,377
Isoelectric Point (pI) 6.14
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIII:50838 to 52340 | ORF Map | GBrowse
Genetic position: -47 cM
Last Update Coordinates: 2000-09-13 | Sequence: 1997-01-28
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1503 50838..52340 2000-09-13 1997-01-28
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 SGDIDS000000545

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 (6, 7, 8). All three proteins are involved in the uptake of glucose (1), however Hxk2p appears to play the main role during glucose phosphorylation in vivo, because it is the predominant isoenzyme during growth on glucose (6, 8). The HXK2 gene is expressed when yeast cells are grown on a fermentable medium using glucose, fructose or mannose as a carbon source (1, 9). 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 (10, 4).

Both Hxk1p and Glk1p are found in the cytosol (11), whereas Hxk2p shows both cytoplasmic and nuclear localization (12). Cytoplasmic Hxk2p is a key enzyme in glycolysis, whereas nuclear Hxk2p is involved in signaling the glucose-induced repression of the HXK1 and GLK1 genes and glucose-induced expression of its own gene, HXK2 (4, 13, 14).

HXK1, HXK2, and GLK1 homologs have been identified in fission yeast, rice, arabidopsis, and mammals (15, 16, 17). 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) (18).

Last updated: 2006-11-29 Contact SGD

References cited on this page View Complete Literature Guide for GLK1
1) 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
2) Hirayama T, et al.  (1995) Cloning and characterization of seven cDNAs for hyperosmolarity-responsive (HOR) genes of Saccharomyces cerevisiae. Mol Gen Genet 249(2):127-38
3) Herrero P, et al.  (1995) Transcriptional regulation of the Saccharomyces cerevisiae HXK1, HXK2 and GLK1 genes. Yeast 11(2):137-44
4) 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
5) 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
6) Walsh RB, et al.  (1983) Cloning of genes that complement yeast hexokinase and glucokinase mutants. J Bacteriol 154(2):1002-4
7) Clifton D, et al.  (1993) Functional studies of yeast glucokinase. J Bacteriol 175(11):3289-94
8) 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
9) 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
10) Lobo Z and Maitra PK  (1977) Physiological role of glucose-phosphorylating enzymes in Saccharomyces cerevisiae. Arch Biochem Biophys 182(2):639-45
11) Alberts B, et al.  (1994) Molecular Biology of the Cell (3rd ed.). New York: Garland Publishing
12) Randez-Gil F, et al.  (1998) Hexokinase PII has a double cytosolic-nuclear localisation in Saccharomyces cerevisiae. FEBS Lett 425(3):475-8
13) Gancedo JM  (1998) Yeast carbon catabolite repression. Microbiol Mol Biol Rev 62(2):334-61
14) Johnston M  (1999) Feasting, fasting and fermenting. Glucose sensing in yeast and other cells. Trends Genet 15(1):29-33
15) 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
16) 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
17) 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
18) 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