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Hsf1p binds in both constitutive and inducible manners to the conserved heat shock element (HSE) motif found in the promoters of its target genes as a homotrimeric complex; each individual monomer recognizes the 5-bp sequence, 5'-NGAAN-3' (1, 26, 28). HSEs fall into one of three categories depending on the organization of the NGAAN motifs: ''Perfect'' HSEs consist of three or more contiguous repeats of the motif, ''gap'' HSEs consists of a 5-bp gap separating two contiguous motifs from a third one, and ''step'' HSEs contain 5-bp gaps separating each of the three motifs (5 and references contained therein).In unstressed cells Hsf1p is constitutively phosphorylated, but under certain stresses, such as alkaline pH, increased concentrations of salicylate, oxidative stress, heat stress, or glucose starvation, it becomes hyperphosphorylated and adopts an activated conformation resulting in the transcription of target genes (14, and reviewed in 15). Glucose starvation-induced hyperphosphorylation is mediated by the AMP-activated kinase Snf1p (18).

Hsf1p includes a winged-helix-turn-helix DNA-binding domain (DBD) (19), a hydrophobic repeat region necessary for coiled-coil formation during Hsf1p oligomerization (21), N-terminal and C-terminal trans-activation domains (AR1 and AR2) (22, 25), the negative regulatory domain conserved element 2 (CE2) (27), and the C-terminal modulator (CTM) domain which alleviates CE2 repression (29). In addition to binding HSE motifs, the DBD negatively regulates Hsf1p transcriptional activity (4). AR1 is thought to mediate the response to transient heat shock while AR2 is thought to mediate response to sustained heat stress (25). AR2 and CTM are also necessary for mediating transcription of genes with gap-type HSEs (29, 30).

The general structure and function of heat shock factors are conserved between eukaryotic organisms, but the number and importance of HSF genes varies. HSF1 homologs have been identified in S. pombe, D. melanogaster, chickens, plants, and mammals (17 and references therein). Mammalian HSF1 is involved in the processes of stress-induced transcription, extra-embryonic development, and postnatal growth (31).", "date_edited": "2006-11-13"}, "literature_overview": {"primary_count": 155, "additional_count": 173, "review_count": 82, "go_count": 12, "phenotype_count": 15, "disease_count": 0, "interaction_count": 55, "regulation_count": 14, "ptm_count": 11, "funComplement_count": 1, "htp_count": 22, "total_count": 459}, "disease_overview": {"manual_disease_terms": [], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": null}, "ecnumbers": [], "URS_ID": null, "main_strain": "S288C", "regulation_overview": {"regulator_count": 11, "target_count": 479, "paragraph": {"text": "HSF1 encodes an evolutionarily conserved winged helix-turn-helix transcription factor of the E2F family that binds 5'-ATGGAACR-3' sequence motifs. Hsf1p is involved in upregulating the transcription of heat-shock-responsive genes after robust increases in temperature. Hsf1p contains a DNA-binding domain, three leucine zipper repeats responsible for Hsf1p trimerization, a C-terminal transactivation domain, and an N-terminal transactivation domain. All Hsf1p target gene promoters contain multiples of the pentameric sequence 5'-NGAAN-3', termed heat shock elements (HSEs). Hsf1p recognizes both continuous and discontinuous repeats of HSEs. The active DNA-binding form of Hsf1p is a homotrimer. While each HSE is a recognition site for a single Hsf1p monomer, a minimum of three pentameric units is required for stable binding. Some target genes contain four to six contiguous HSEs that are bound by two Hsf1p homotrimers, or seven to eight units that may recruit up to three colocalized homotrimers. However, a single Hsf1p trimer is sufficient to activate transcription. Hsf1p is constitutively bound on target promoters as a homotrimer even in the absence of stress, and its activation function is modulated at the post-translational level. Hsf1p is rapidly phosphorylated after heat shock, and conversion of Hsf1p into the active form occurs simultaneously with extensive phosphorylation. Hsf1 is phosphorylated at different phosphor-acceptor sites in response to heat or menadione, suggesting stress-specific phosphorylation. Hyperphosphorylation generally correlates with the transactivation of Hsf1p, though some phosphorylation events repress its transcriptional activity. Hsf1p is likely phosphorylated by one or more serine-threonine protein kinases, such as Snf1p and/or Yak1p. The Hsp70/Hsp90 chaperone complex appears to repress the transcriptional activation activity of Hsf1p under nonstress conditions. During heat shock, the accumulation of unfolded or damaged proteins may titrate the chaperone machinery from Hsf1p, allowing the derepression of Hsf1p.", "date_edited": "2016-10-15", "references": [{"id": 398761, "display_name": "Simpson CE and Ashe MP (2012)", "citation": "Simpson CE and Ashe MP (2012) Adaptation to stress in yeast: to translate or not? Biochem Soc Trans 40(4):794-9", "pubmed_id": 22817736, "link": "/reference/S000150324", "year": 2012, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1042/BST20120078"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/22817736"}]}, {"id": 401124, "display_name": "Verghese J, et al. (2012)", "citation": "Verghese J, et al. (2012) Biology of the heat shock response and protein chaperones: budding yeast (Saccharomyces cerevisiae) as a model system. Microbiol Mol Biol Rev 76(2):115-58", "pubmed_id": 22688810, "link": "/reference/S000149794", "year": 2012, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1128/MMBR.05018-11"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372250/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/22688810"}]}]}}, "reference_mapping": {"635985": 1, "538236": 2, "538486": 3, "542830": 4, "535156": 5, "542854": 6, "392849": 7, "387856": 8, "614996": 9, "2222140": 10, "2502519": 11, "2473357": 12, "579352": 13, "525744": 14, "524669": 15, "528171": 16, "514354": 17, "545634": 18, "570318": 19, "530847": 20, "579355": 21, "597321": 22, "607863": 23, "632025": 24, "597324": 25, "631269": 26, "542789": 27, "616188": 28, "586652": 29, "602552": 30, "510623": 31, "644894": 32}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: EXA3", "date_created": "2010-02-16", "references": [{"id": 644894, "display_name": "Nelson RJ, et al. (1992)", "citation": "Nelson RJ, et al. (1992) Isolation and characterization of extragenic suppressors of mutations in the SSA hsp70 genes of Saccharomyces cerevisiae. Genetics 131(2):277-85", "pubmed_id": 1644272, "link": "/reference/S000040736", "year": 1992, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1093/genetics/131.2.277"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1205003/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/1644272"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: HSF1", "date_created": "2000-05-19", "references": [{"id": 635985, "display_name": "Wiederrecht G, et al. (1988)", "citation": "Wiederrecht G, et al. (1988) Isolation of the gene encoding the S. cerevisiae heat shock transcription factor. Cell 54(6):841-53", "pubmed_id": 3044612, "link": "/reference/S000043737", "year": 1988, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/s0092-8674(88)91197-x"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/3044612"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: MAS3", "date_created": "2010-02-16", "references": []}], "complexes": []}, tabs: {"id": 1267031, "protein_tab": true, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": true, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": true, "disease_tab": false} }; HSF1 | SGD

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HSF1 / YGL073W Overview

Standard Name
HSF1 1
Systematic Name
YGL073W
SGD ID
SGD:S000003041
Aliases
EXA3 32 , MAS3
Feature Type
ORF , Verified
Description
Trimeric heat shock transcription factor; forms condensate with Mediator and RNA Pol II upon heat shock; activates multiple genes in response to diverse stresses and transient intracellular acidification; recognizes variable heat shock elements (HSEs) consisting of inverted NGAAN repeats; monitors translational status through RQC (Ribosomal Quality Control)-mediated translation-stress signal; human homolog HSF1 with linker region mutations can complement yeast hsf1 mutant 2 3 4 5 7 8 9 10 11 12
Name Description
Heat Shock transcription Factor 6
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.

Summary
HSF1/YGL073W is located on the left arm of chromosome VII between MPS2 and AFT1 transcription factor; coding sequence is 2502 nucleotides long with 24 SNPs, 10 of which cause amino acid polymorphisms

Analyze Sequence

S288C only

BLASTN | BLASTP | Design Primers | Restriction Fragment Map | Restriction Fragment Sizes | Six-Frame Translation

S288C vs. other species

BLASTN vs. fungi | BLASTP at NCBI | BLASTP vs. fungi

S288C vs. other strains

Strain Alignment | Variant Viewer

Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.

Summary
Hsf1p is 833 amino acids long, of average half-life, low in abundance; contains disordered regions throughout protein and 3 heat shock factor (HSF)-type DNA-binding domains; acetylated on K219, phosphorylated on 27 residues
Length (a.a.)
833
Mol. Weight (Da)
93253.3
Isoelectric Point
5.06
Median Abundance (molecules/cell)
2222 +/- 1099
Half-life (hr)
10.4

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.

View all HSF1 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.

Summary
Sequence-specific DNA binding transcription factor that induces expression of the Hsp90-family protein chaperones Hsc82p and Hsp82p during the cellular response to heat; also negatively regulates TOR signaling

View computational annotations

Molecular Function

Manually Curated

Biological Process

Manually Curated

Cellular Component

Manually Curated
Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.

Summary
HSF1/YGL073W is an essential gene, null mutants are inviable; overexpression arrests growth in haploid, increases invasive growth in diploid; reduced function decreases resistance to TOR innibitor rapamycin, increases competitive fitness; conditional alleles confer sensitivity to heat and to microtubule-destabilising agent benomyl; R206S substitution makes protein constitutively active

Classical Genetics

overexpression
conditional
null
activation
reduction of function

Large-scale Survey

null
overexpression
reduction of function
conditional
Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.

Summary
Hsf1p interacts physically with proteins involved in transcription; HSF1 interacts genetically with genes involved in mitotic cell cycle

559 total interactions for 423 unique genes

Physical Interactions

  • Affinity Capture-MS: 23
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 12
  • Biochemical Activity: 13
  • Co-localization: 4
  • Protein-peptide: 1
  • Proximity Label-MS: 3
  • Reconstituted Complex: 7
  • Two-hybrid: 4

Genetic Interactions

  • Dosage Rescue: 16
  • Negative Genetic: 379
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 6
  • Positive Genetic: 62
  • Synthetic Growth Defect: 3
  • Synthetic Haploinsufficiency: 2
  • Synthetic Lethality: 6
  • Synthetic Rescue: 12
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.

Summary
HSF1 encodes an evolutionarily conserved winged helix-turn-helix transcription factor of the E2F family that binds 5'-ATGGAACR-3' sequence motifs. Hsf1p is involved in upregulating the transcription of heat-shock-responsive genes after robust increases in temperature. Hsf1p contains a DNA-binding domain, three leucine zipper repeats responsible for Hsf1p trimerization, a C-terminal transactivation domain, and an N-terminal transactivation domain. All Hsf1p target gene promoters contain multiples of the pentameric sequence 5'-NGAAN-3', termed heat shock elements (HSEs). Hsf1p recognizes both continuous and discontinuous repeats of HSEs. The active DNA-binding form of Hsf1p is a homotrimer. While each HSE is a recognition site for a single Hsf1p monomer, a minimum of three pentameric units is required for stable binding. Some target genes contain four to six contiguous HSEs that are bound by two Hsf1p homotrimers, or seven to eight units that may recruit up to three colocalized homotrimers. However, a single Hsf1p trimer is sufficient to activate transcription. Hsf1p is constitutively bound on target promoters as a homotrimer even in the absence of stress, and its activation function is modulated at the post-translational level. Hsf1p is rapidly phosphorylated after heat shock, and conversion of Hsf1p into the active form occurs simultaneously with extensive phosphorylation. Hsf1 is phosphorylated at different phosphor-acceptor sites in response to heat or menadione, suggesting stress-specific phosphorylation. Hyperphosphorylation generally correlates with the transactivation of Hsf1p, though some phosphorylation events repress its transcriptional activity. Hsf1p is likely phosphorylated by one or more serine-threonine protein kinases, such as Snf1p and/or Yak1p. The Hsp70/Hsp90 chaperone complex appears to repress the transcriptional activation activity of Hsf1p under nonstress conditions. During heat shock, the accumulation of unfolded or damaged proteins may titrate the chaperone machinery from Hsf1p, allowing the derepression of Hsf1p.
Regulators
11
Targets
479
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.

Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.

Last Updated: 2006-11-13

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.

Primary
155
Additional
173
Reviews
82

Resources

AlphaFold Protein Structure | Entrez Gene | Entrez RefSeq Protein | FungiDB | Search all NCBI | UniParc | UniProtKB