GAL4/YPL248C Summary Help

Standard Name GAL4 1, 2
Systematic Name YPL248C
Alias GAL81 3
Feature Type ORF, Verified
Description DNA-binding transcription factor required for activating GAL genes; responds to galactose; repressed by Gal80p and activated by Gal3p (4 and see Summary Paragraph)
Name Description GALactose metabolism
Chromosomal Location
ChrXVI:82356 to 79711 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -143 cM
Gene Ontology Annotations All GAL4 GO evidence and references
  View Computational GO annotations for GAL4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 43 genes
Regulators 3 genes
Classical genetics
reduction of function
Large-scale survey
194 total interaction(s) for 86 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 35
  • Biochemical Activity: 4
  • Co-crystal Structure: 3
  • Co-localization: 15
  • Co-purification: 1
  • Far Western: 1
  • FRET: 1
  • PCA: 34
  • Protein-peptide: 1
  • Reconstituted Complex: 47
  • Two-hybrid: 13

Genetic Interactions
  • Dosage Lethality: 1
  • Dosage Rescue: 2
  • Negative Genetic: 18
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 4
  • Positive Genetic: 7
  • Synthetic Rescue: 4

Expression Summary
Length (a.a.) 881
Molecular Weight (Da) 99,402
Isoelectric Point (pI) 7.14
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXVI:82356 to 79711 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: -143 cM
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2646 82356..79711 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 | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000006169

GAL4 encodes the archetypal member of the Zn(II)2Cys6 family, also called the zinc cluster family, of transcriptional regulators; there are approximately 46 proteins of this family in S. cerevisiae (reviewed in 5 and 6). Gal4p mediates expression of most of the genes involved in utilization of galactose, a relatively poor carbon source that is used only if glucose or other carbon sources are not available. Galactose induces expression of the Gal4p-regulated genes, which include the galactose utilization genes GAL1, GAL2, GAL3, GAL7, GAL10, and GAL80 as well as GCY1, LAP3, MTH1, PCL10, REE1, and FUR4 (7, 8, 9). Gal4p-regulated genes contain upstream activating sequences (UASGAL) in their promoter regions to which Gal4p binds; when galactose is present as the sole carbon source, bound Gal4p recruits the transcription machinery to actively transcribe these genes (10). The number of UASGAL sites in the promoters of the genes varies, which plays a role in the extent of activation possible; induction of GAL1, GAL2, GAL7, and GAL10 is over 1000-fold (10, reviewed in 11).

When cells are grown in glucose as carbon source, GAL4 transcription is reduced roughly 5-fold, a modest decrease that nevertheless has a large repressive effect on transcription of genes under Gal4p control (12). Growth in the presence of other carbon sources, such as raffinose, allows production of Gal4p, but its activity is inhibited through interaction with Gal80p, which blocks the surface of Gal4p that interacts with the transcription machinery; this Gal4p-Gal80p complex is tethered to upstream activating sequences of the GAL genes through the DNA binding region of Gal4p (reviewed in 13 and 11). When cells are fed galactose, the galactose sensor protein Gal3p enters the nucleus and binds to Gal80p (14). As the Gal3p-Gal80p complex (but not uncomplexed Gal80p) can be identified in both the cytoplasm and the nucleus, the Gal3p-Gal80p interaction may help prevent further interaction between Gal80p and Gal4p (14). Active Gal4p recruits the SAGA complex, Mediator complex, and other components of the transcriptional machinery to initiate transcription (15, 16, 17).

Activation by Gal4p relies on an acidic C-terminal region that both stimulates transcription and also binds Gal80p (18, 19, 20). In addition to its interactions with the transcription machinery, this acidic activating domain (AD) interacts with Sug1p and Sug2p, subunits of the 19S regulatory particle of the 26S proteasome (reviewed in 13), and is a site of monoubiquitylation (21, 22). Gal4p binds the UASGAL site as a dimer, and both DNA binding and dimerization are mediated by sequences in the N-terminal region (23). Gal4p also undergoes phosphorylation during activation, although studies indicate this phosphorylation is not essential for activity (13). The DNA binding domain of Gal4p can be physically separated from its transcription activation domain; thus these domains have been used in the development of tools, such as the two-hybrid assay, for studies of transcription regulation and protein-protein interactions (reviewed in 24).

While proteins containing Zn(II)2Cys6 motifs are found in S. cerevisiae and other fungi, they have not been identified in prokaryotes or higher eukaryotes (reviewed in 6).

Last updated: 2010-12-01 Contact SGD

References cited on this page View Complete Literature Guide for GAL4
1) Haber, J.  (1985) Personal Communication, Mortimer Map Edition 9
2) Link, A. and Olson, M.  (1989) Personal Communication, Mortimer Map Edition 10
3) Hopper JE and Rowe LB  (1978) Molecular expression and regulation of the galactose pathway genes in Saccharomyces cerevisiae. Distinct messenger RNAs specified by the Gali and Gal7 genes in the Gal7-Gal10-Gal1 cluster. J Biol Chem 253(20):7566-9
4) Bhat PJ and Murthy TV  (2001) Transcriptional control of the GAL/MEL regulon of yeast Saccharomyces cerevisiae: mechanism of galactose-mediated signal transduction. Mol Microbiol 40(5):1059-66
5) MacPherson S, et al.  (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70(3):583-604
6) Campbell RN, et al.  (2008) Metabolic control of transcription: paradigms and lessons from Saccharomyces cerevisiae. Biochem J 414(2):177-87
7) Ren B, et al.  (2000) Genome-wide location and function of DNA binding proteins. Science 290(5500):2306-9
8) Zheng W, et al.  (1997) The cysteine-peptidase bleomycin hydrolase is a member of the galactose regulon in yeast. J Biol Chem 272(48):30350-5
9) Choi ID, et al.  (2008) Novel Ree1 regulates the expression of ENO1 via the Snf1 complex pathway in Saccharomyces cerevisiae. Biochem Biophys Res Commun 377(2):395-9
10) Bram RJ, et al.  (1986) A GAL family of upstream activating sequences in yeast: roles in both induction and repression of transcription. EMBO J 5(3):603-8
11) Sellick CA, et al.  (2008) Chapter 3 galactose metabolism in yeast-structure and regulation of the leloir pathway enzymes and the genes encoding them. Int Rev Cell Mol Biol 269:111-50
12) Griggs DW and Johnston M  (1991) Regulated expression of the GAL4 activator gene in yeast provides a sensitive genetic switch for glucose repression. Proc Natl Acad Sci U S A 88(19):8597-601
13) Traven A, et al.  (2006) Yeast Gal4: a transcriptional paradigm revisited. EMBO Rep 7(5):496-9
14) Wightman R, et al.  (2008) Localization and Interaction of the Proteins Constituting the GAL Genetic Switch in Saccharomyces cerevisiae. Eukaryot Cell 7(12):2061-2068
15) Lemieux K and Gaudreau L  (2004) Targeting of Swi/Snf to the yeast GAL1 UAS G requires the Mediator, TAF IIs, and RNA polymerase II. EMBO J 23(20):4040-50
16) Prather DM, et al.  (2005) Evidence that the elongation factor TFIIS plays a role in transcription initiation at GAL1 in Saccharomyces cerevisiae. Mol Cell Biol 25(7):2650-9
17) Bhaumik SR, et al.  (2004) In vivo target of a transcriptional activator revealed by fluorescence resonance energy transfer. Genes Dev 18(3):333-43
18) Ma J and Ptashne M  (1987) Deletion analysis of GAL4 defines two transcriptional activating segments. Cell 48(5):847-53
19) Ma J and Ptashne M  (1987) The carboxy-terminal 30 amino acids of GAL4 are recognized by GAL80. Cell 50(1):137-42
20) Johnston SA, et al.  (1987) Interaction of positive and negative regulatory proteins in the galactose regulon of yeast. Cell 50(1):143-6
21) Chang C, et al.  (2001) The Gal4 activation domain binds Sug2 protein, a proteasome component, in vivo and in vitro. J Biol Chem 276(33):30956-63
22) Archer CT, et al.  (2008) Activation Domain-dependent Monoubiquitylation of Gal4 Protein Is Essential for Promoter Binding in Vivo. J Biol Chem 283(18):12614-23
23) Baleja JD, et al.  (1992) Solution structure of the DNA-binding domain of Cd2-GAL4 from S. cerevisiae. Nature 356(6368):450-3
24) Brent R and Finley RL Jr  (1997) Understanding gene and allele function with two-hybrid methods. Annu Rev Genet 31:663-704
25) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
26) Zhu J and Zhang MQ  (1999) SCPD: a promoter database of the yeast Saccharomyces cerevisiae. Bioinformatics 15(7-8):607-11
27) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66