MSN2/YMR037C Summary Help

Standard Name MSN2 1
Systematic Name YMR037C
Feature Type ORF, Verified
Description Stress-responsive transcriptional activator; activated in stress conditions, which results in translocation from cytoplasm to nucleus; transported back to cytoplasm once stress is removed; binds DNA at stress response elements of responsive genes, inducing gene expression; relative distribution to nucleus increases upon DNA replication stress; MSN2 has a paralog, MSN4, that arose from the whole genome duplication (2, 3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description Multicopy suppressor of SNF1 mutation 1
Chromosomal Location
ChrXIII:346517 to 344403 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All MSN2 GO evidence and references
  View Computational GO annotations for MSN2
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Targets 381 genes
Regulators 2 genes
Resources
Classical genetics
null
overexpression
Large-scale survey
null
overexpression
Resources
188 total interaction(s) for 122 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 5
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 5
  • Biochemical Activity: 6
  • Co-localization: 7
  • PCA: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 4

Genetic Interactions
  • Dosage Growth Defect: 3
  • Dosage Lethality: 1
  • Dosage Rescue: 12
  • Negative Genetic: 81
  • Phenotypic Enhancement: 23
  • Phenotypic Suppression: 10
  • Positive Genetic: 4
  • Synthetic Growth Defect: 10
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 2
  • Synthetic Rescue: 9

Resources
Expression Summary
histogram
Resources
Length (a.a.) 704
Molecular Weight (Da) 77,860
Isoelectric Point (pI) 6.55
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:346517 to 344403 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..2115 346517..344403 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004640
SUMMARY PARAGRAPH for MSN2

MSN2 and MSN4 encode transcription factors that regulate the general stress response of S. cerevisiae (2, 8). Msn2p and Msn4p regulate the expression of ~200 genes in response to several stresses, including heat shock, osmotic shock, oxidative stress, low pH, glucose starvation, sorbic acid and high ethanol concentrations, by binding to the STRE element, 5'-CCCCT-3', located in the promoters of these genes (2, 9, 10). MSN4 gene expression is itself Msn2/4p dependent and induced by stress, while MSN2 expression is constitutive (9).

Msn2p and Msn4p are largely, but not completely, functionally redundant and there is increasing evidence that the individual regulatory contributions of these transcription factors differ for specific genes and under particular stress conditions (reviewed in 11). The two proteins share 41% identity and are similar in size and amino acid composition (1). While single deletion mutants of msn2 and msn4 have no obvious phenotype, msn2msn4 double null mutants are hypersensitive to carbon source starvation, heat shock, and osmotic and oxidative stresses and overexpression of MSN2 and MSN4 genes decreases sensitivity to starvation and thermal stresses (1 and reviewed in 11).

In their N-terminal halves, Msn2/4p contain transcription-activating domains and a nuclear export sequence (12, 13). At the C-terminus, both proteins contain a zinc-finger binding domain that recognizes the STRE element (2, 8). DNA binding by Msn2p is thought to be regulated by stress and by the kinases cAMP-dependent protein kinase (PKA, composed of Tpk1p, Tpk2p, and Tpk3p and regulatory subunit Bcy1p) and Gsk3p (3, 14). Adjacent to the zinc-finger, Msn2p and Msn4p each contain a nuclear localization signal, which is inhibited by PKA phosphorylation and activated by protein phosphatase 1 dephosphorylation (13, 3, 15).

Under non-stress conditions, Msn2p and Msn4p are located in the cytoplasm (3). Cytoplasmic localization is partially regulated by TOR signalling with the 14-3-3 protein Bmh2p acting as a cytoplasmic anchoring partner for Msn2/4p (16). Upon stress, Msn2/4p are hyperphosphorylated, relocalized to the nucleus and then display a periodic nucleocytoplasmic shuttling behavior (3, 17, 18). Nuclear export of Msn2p has been shown to be dependent on the exportin Msn5p and nuclear localization at both the import and export level is regulated by PKA (3, 13, 18). Msn2p is also positively regulated by the Psr1p/Whi2p phosphatase complex and negatively regulated by Snf1p phosphorylation and by its degradation in the nucleus, a process dependent on the cyclin-dependent kinase Ssn3p (19, 15, 20).

Genes similar to MSN2/4 have been identified in Schizosaccharomyces pombe, Trichoderma atroviride, and Candida albicans (21, 22, 23). However, the C. albicans Msn2- and Msn4-like proteins do not appear to play a significant role in the stress response of this fungal pathogen (23).

Last updated: 2007-01-17 Contact SGD

References cited on this page View Complete Literature Guide for MSN2
1) Estruch F and Carlson M  (1993) Two homologous zinc finger genes identified by multicopy suppression in a SNF1 protein kinase mutant of Saccharomyces cerevisiae. Mol Cell Biol 13(7):3872-81
2) Martinez-Pastor MT, et al.  (1996) The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 15(9):2227-35
3) Gorner W, et al.  (1998) Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev 12(4):586-97
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) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
6) Petrenko N, et al.  (2013) Noise and interlocking signaling pathways promote distinct transcription factor dynamics in response to different stresses. Mol Biol Cell 24(12):2045-57
7) Sunnaker M, et al.  (2013) Automatic generation of predictive dynamic models reveals nuclear phosphorylation as the key msn2 control mechanism. Sci Signal 6(277):ra41
8) Schmitt AP and McEntee K  (1996) Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 93(12):5777-82
9) Gasch AP, et al.  (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11(12):4241-57
10) Causton HC, et al.  (2001) Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12(2):323-37
11) Estruch F  (2000) Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 24(4):469-86
12) Boy-Marcotte E, et al.  (2006) The transcriptional activation region of Msn2p, in Saccharomyces cerevisiae, is regulated by stress but is insensitive to the cAMP signalling pathway. Mol Genet Genomics 275(3):277-87
13) Gorner W, et al.  (2002) Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor. EMBO J 21(1-2):135-44
14) Hirata Y, et al.  (2003) Yeast glycogen synthase kinase-3 activates Msn2p-dependent transcription of stress responsive genes. Mol Biol Cell 14(1):302-12
15) De Wever V, et al.  (2005) A dual role for PP1 in shaping the Msn2-dependent transcriptional response to glucose starvation. EMBO J 24(23):4115-23
16) Beck T and Hall MN  (1999) The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402(6762):689-92
17) Garreau H, et al.  (2000) Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae. Microbiology 146 ( Pt 9)():2113-20
18) Jacquet M, et al.  (2003) Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in Saccharomyces cerevisiae. J Cell Biol 161(3):497-505
19) Kaida D, et al.  (2002) Yeast Whi2 and Psr1-phosphatase form a complex and regulate STRE-mediated gene expression. Genes Cells 7(6):543-52
20) Bose S, et al.  (2005) Genetic factors that regulate the attenuation of the general stress response of yeast. Genetics 169(3):1215-26
21) Kunitomo H, et al.  (2000) A zinc-finger protein, Rst2p, regulates transcription of the fission yeast ste11(+) gene, which encodes a pivotal transcription factor for sexual development. Mol Biol Cell 11(9):3205-17
22) Peterbauer CK, et al.  (2002) The Trichoderma atroviride seb1 (stress response element binding) gene encodes an AGGGG-binding protein which is involved in the response to high osmolarity stress. Mol Genet Genomics 268(2):223-31
23) Nicholls S, et al.  (2004) Msn2- and Msn4-like transcription factors play no obvious roles in the stress responses of the fungal pathogen Candida albicans. Eukaryot Cell 3(5):1111-23
24) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
25) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87