CUP1-1/YHR053C Summary Help

Standard Name CUP1-1
Systematic Name YHR053C
Alias CUP1
Feature Type ORF, Verified
Description Metallothionein; binds copper and mediates resistance to high concentrations of copper and cadmium; locus is variably amplified in different strains, with two copies, CUP1-1 and CUP1-2, in the genomic sequence reference strain S288C; CUP1-1 has a paralog, CUP1-2, that arose from a segmental duplication (1, 2, 3 and see Summary Paragraph)
Chromosomal Location
ChrVIII:212720 to 212535 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All CUP1-1 GO evidence and references
  View Computational GO annotations for CUP1-1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 16 genes
Classical genetics
11 total interaction(s) for 8 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 2
  • Affinity Capture-RNA: 2
  • Co-purification: 1
  • PCA: 1

Genetic Interactions
  • Dosage Rescue: 2
  • Phenotypic Suppression: 1
  • Synthetic Lethality: 2

Expression Summary
Length (a.a.) 61
Molecular Weight (Da) 6,650
Isoelectric Point (pI) 5.79
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVIII:212720 to 212535 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
This feature is contained within: RUF5-1
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..186 212720..212535 2011-02-03 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 SGDIDS000001095

As the major copper-activated metallothionine in yeast, Cup1p binds and sequesters cuprous copper(I), Cu+, providing the principal method of removing this metal ion from the cell (4, 5, 6). Careful control of copper ion homeostasis is important because trace concentrations are essential for yeast survival, while high concentrations are toxic (see 7 for review). CUP1 transcription is specifically induced by the copper-dependent transcription activator Cup2p (more commonly known as Ace1p) in response to high levels of copper ions (8, 9, 10) and by Hsf1p in response to heat shock, glucose starvation and oxidation stress (11, reviewed in 12). In the presence of copper, Cup1p is also capable of antioxidant activity and thus contributes a significant, albeit minor, role to oxygen radical detoxification, especially in the absence of Cu,Zn-superoxide dismutase Sod1p (13, 14).

Although Cup1p is capable of binding other metal ions in vitro (1), it is responsible only for copper and cadmium ion tolerance in vivo, and the resistance to Cd++ ions is only observed at high copy number or when CUP1 is overexpressed (15, 16). This is in contrast to the metallothioneins found higher eukaryotes, which are typically capable of detoxifying an array of metal ions.

Naturally occurring tandem duplications of the CUP1 gene are common, and it is typically found in arrays of 2-20 copies per CUP1 locus. In general, the higher the copy number, the greater the copper ion tolerance, and strains containing only one copy are considered to be copper ion sensitive (17). Most lab strains contain two copies, and these are designated as CUP1-1 and CUP1-2 in the reference strain (S288C) (2).

CUP1 is notable not just for its role in the biology of yeast, but also for its extensive use as a tool in molecular biology. Most importantly, the copper inducible CUP1 promoter is widely used in expression systems (e.g., 18, 19, 20, 21, 22 and briefly reviewed in 23). The CUP1 gene has also been put to use in a wide array of other applications, including as a selectable marker (e.g., 24), as a construct to study intron splicing (25), and as the reporter in a two hybrid assay (26).

Last updated: 2010-05-18 Contact SGD

References cited on this page View Complete Literature Guide for CUP1-1
1) Winge DR, et al.  (1985) Yeast metallothionein. Sequence and metal-binding properties. J Biol Chem 260(27):14464-70
2) Karin M, et al.  (1984) Primary structure and transcription of an amplified genetic locus: the CUP1 locus of yeast. Proc Natl Acad Sci U S A 81(2):337-41
3) Katju V, et al.  (2009) Variation in gene duplicates with low synonymous divergence in Saccharomyces cerevisiae relative to Caenorhabditis elegans. Genome Biol 10(7):R75
4) Butt TR, et al.  (1984) Cloning and expression of a yeast copper metallothionein gene. Gene 27(1):23-33
5) Butt TR, et al.  (1984) Copper metallothionein of yeast, structure of the gene, and regulation of expression. Proc Natl Acad Sci U S A 81(11):3332-6
6) Jensen LT, et al.  (1996) Enhanced effectiveness of copper ion buffering by CUP1 metallothionein compared with CRS5 metallothionein in Saccharomyces cerevisiae. J Biol Chem 271(31):18514-9
7) Rutherford JC and Bird AJ  (2004) Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryot Cell 3(1):1-13
8) Thiele DJ  (1988) ACE1 regulates expression of the Saccharomyces cerevisiae metallothionein gene. Mol Cell Biol 8(7):2745-52
9) Welch J, et al.  (1989) The CUP2 gene product regulates the expression of the CUP1 gene, coding for yeast metallothionein. EMBO J 8(1):255-60
10) Buchman C, et al.  (1989) The CUP2 gene product, regulator of yeast metallothionein expression, is a copper-activated DNA-binding protein. Mol Cell Biol 9(9):4091-5
11) Tamai KT, et al.  (1994) Heat shock transcription factor activates yeast metallothionein gene expression in response to heat and glucose starvation via distinct signalling pathways. Mol Cell Biol 14(12):8155-65
12) Mager WH and De Kruijff AJ  (1995) Stress-induced transcriptional activation. Microbiol Rev 59(3):506-31
13) Tamai KT, et al.  (1993) Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase. Proc Natl Acad Sci U S A 90(17):8013-7
14) Liu XD and Thiele DJ  (1996) Oxidative stress induced heat shock factor phosphorylation and HSF-dependent activation of yeast metallothionein gene transcription. Genes Dev 10(5):592-603
15) Ecker DJ, et al.  (1986) Yeast metallothionein function in metal ion detoxification. J Biol Chem 261(36):16895-900
16) Jeyaprakash A, et al.  (1991) Multicopy CUP1 plasmids enhance cadmium and copper resistance levels in yeast. Mol Gen Genet 225(3):363-8
17) Fogel S and Welch JW  (1982) Tandem gene amplification mediates copper resistance in yeast. Proc Natl Acad Sci U S A 79(17):5342-6
18) Etcheverry T  (1990) Induced expression using yeast copper metallothionein promoter. Methods Enzymol 185():319-29
19) Holz C and Lang C  (2004) High-throughput expression in microplate format in Saccharomyces cerevisiae. Methods Mol Biol 267:267-76
20) Wang Z  (2006) Controlled expression of recombinant genes and preparation of cell-free extracts in yeast. Methods Mol Biol 313:317-31
21) Ecker DJ, et al.  (1987) Chemical synthesis and expression of a cassette adapted ubiquitin gene. J Biol Chem 262(8):3524-7
22) Akada R, et al.  (2002) Sets of integrating plasmids and gene disruption cassettes containing improved counter-selection markers designed for repeated use in budding yeast. Yeast 19(5):393-402
23) Maya D, et al.  (2008) Systems for applied gene control in Saccharomyces cerevisiae. Biotechnol Lett 30(6):979-87
24) Hottiger T, et al.  (1995) 2-micron vectors containing the Saccharomyces cerevisiae metallothionein gene as a selectable marker: excellent stability in complex media, and high-level expression of a recombinant protein from a CUP1-promoter-controlled expression cassette in cis. Yeast 11(1):1-14
25) Lesser CF and Guthrie C  (1993) Mutational analysis of pre-mRNA splicing in Saccharomyces cerevisiae using a sensitive new reporter gene, CUP1. Genetics 133(4):851-63
26) Mayer G, et al.  (1999) Application of the green fluorescent protein as a reporter for Ace1-based, two-hybrid studies. Biotechniques 27(1):86-8, 92-4