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HSP104 is expressed at very low levels under normal conditions but is induced upon stress (17). Transcriptional upregulation is independently mediated by the transcriptional activators Msn2p/Msn4p and Hsf1p, which bind to three stress response elements and two heat shock elements present in the HSP104 promoter (19).

Hsp104p is thought to exist in either inactive monomeric, dimeric, or trimeric forms or as an active, ring-shaped hexamer (reviewed in 12). During aggregate disassembly, substrate proteins are unfolded and subsequently threaded through this hexameric ring (21). Formation of the Hsp104p hexamer is nucleotide-dependent and regulated by NBD2, one of two Hsp104p nucleotide-binding domains (NBDs) (reviewed in 12 and 22). Although ATP hydrolysis by NBD2 is slow, ATPase activity of the other NBD, NBD1, is very high and provides the energy necessary to drive protein disaggregation (24). The state of Hsp104p ATP/ADP binding also regulates substrate affinity, with the ADP-bound state having low and the ATP-bound state having high polypeptide affinity (25).HSP104 null mutations result in no obvious phenotype under normal conditions, but when exposed to stresses such as heat, ethanol, and radiation, these mutants have a markedly decreased rate of survival (2, 13). Expression of Hsp78p, the mitochondrial homolog of Hsp104p, in the cytosol of these mutants rescues them from heat damage and restores thermotolerance to the cells (14).

The effect of HSP104 expression has also been studied in yeast models of human disease, such as the prion disease Creutzfeldt-Jakob disease (OMIM) and Huntington disease (OMIM). HSP104 deletion strains are unable to propagate the yeast prions [PSI+], [PIN+], and [URE3] (the mutant protein forms of Sup35p, Rnq1p, and Ure2p, respectively) and it has been shown that both overexpression and underexpression of Hsp104p cures cells carrying the [PSI+] prion (reviewed in 16). Overexpression of HSP104 has been shown to reduce polyglutamine aggregation and toxicity in mammalian cells and to extend the lifespan of transgenic Huntington mice (18 and references contained therein).

Hsp104p homologs have been identified in bacteria, other fungi, and plants (6, 20, 23).", "date_edited": "2006-06-28"}, "literature_overview": {"primary_count": 320, "additional_count": 412, "review_count": 203, "go_count": 12, "phenotype_count": 18, "disease_count": 0, "interaction_count": 154, "regulation_count": 6, "ptm_count": 11, "funComplement_count": 0, "htp_count": 19, "total_count": 1036}, "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": 33, "target_count": 0, "paragraph": {"text": "HSP104 promoter is bound by Bur6p, Fkh2p, Gcn5p, Ncb2p, Rfx1p, Rgr1p, Spt6p, Spt7p, Srb5p, Sua7p, Tfc7p, Tup1p, and Xbp1p in response to heat; HSP104 transcription is regulated by Sfp1p in response to stress; HSP104 transcription is upregulated by Hsf1p in response to heat", "date_edited": "2024-02-13", "references": [{"id": 414327, "display_name": "Venters BJ, et al. (2011)", "citation": "Venters BJ, et al. (2011) A comprehensive genomic binding map of gene and chromatin regulatory proteins in Saccharomyces. Mol Cell 41(4):480-92", "pubmed_id": 21329885, "link": "/reference/S000145602", "year": 2011, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/j.molcel.2011.01.015"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057419/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/21329885"}]}, {"id": 487432, "display_name": "Cipollina C, et al. (2008)", "citation": "Cipollina C, et al. (2008) Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis. Microbiology (Reading) 154(Pt 6):1686-1699", "pubmed_id": 18524923, "link": "/reference/S000126606", "year": 2008, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1099/mic.0.2008/017392-0"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/18524923"}]}, {"id": 535156, "display_name": "Yamamoto A, et al. (2005)", "citation": "Yamamoto A, et al. (2005) Identification of a novel class of target genes and a novel type of binding sequence of heat shock transcription factor in Saccharomyces cerevisiae. J Biol Chem 280(12):11911-9", "pubmed_id": 15647283, "link": "/reference/S000080382", "year": 2005, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1074/jbc.M411256200"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/15647283"}]}]}}, "reference_mapping": {"598167": 1, "640924": 2, "624668": 3, "622588": 4, "615804": 5, "607512": 6, "590648": 7, "398398": 8, "372694": 9, "2280942": 10, "2578899": 11, "523483": 12, "611735": 13, "616766": 14, "571929": 15, "529868": 16, "641266": 17, "527543": 18, "560241": 19, "524533": 20, "541885": 21, "524669": 22, "645507": 23, "563624": 24, "528833": 25}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: HSP104", "date_created": "2000-05-19", "references": [{"id": 598167, "display_name": "Mortimer RK, et al. (1992)", "citation": "Mortimer RK, et al. (1992) Genetic and physical maps of Saccharomyces cerevisiae, Edition 11. Yeast 8(10):817-902", "pubmed_id": 1413997, "link": "/reference/S000056506", "year": 1992, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1002/yea.320081002"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/1413997"}]}]}], "complexes": [{"format_name": "CPX-1861", "display_name": "GET4-GET5 transmembrane domain recognition complex"}]}, tabs: {"id": 1288373, "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} }; HSP104 | SGD

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HSP104 / YLL026W Overview

Standard Name
HSP104 1
Systematic Name
YLL026W
SGD ID
SGD:S000003949
Feature Type
ORF , Verified
Description
Disaggregase; heat shock protein that cooperates with Ydj1p (Hsp40) and Ssa1p (Hsp70) to refold and reactivate denatured, protein aggregates; responds to stresses (heat, ethanol, and sodium arsenite); required for the protein aggregate solid-to-liquid phase transition and dispersal of liquid condensates; involved in [PSI+] propagation; potentiated variants eliminate TDP-43 cytoplasmic aggregates to reduce proteotoxicity; becomes more abundant and forms cytoplasmic foci during replication stress 2 3 4 5 6 7 8 9 10 11
Name Description
Heat Shock Protein 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
HSP104 is located on the left arm of chromosome XII between mitochondrial iron-sulfur cluster binding protein ISA1 and replication origin ARS1206; coding sequence is 753 nucleotides long with 11 SNPs, 6 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
Hsp104p is 908 amino acids long, long-lived, high in abundance; acetylated on 7 lysines, phosphorylated on 26 residues, succinylated on K302 and K442, ubiquitinylated on 7 lysines
Length (a.a.)
908
Mol. Weight (Da)
102009.9
Isoelectric Point
5.1
Median Abundance (molecules/cell)
35086 +/- 12172
Half-life (hr)
23.7

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.

HSP104-KT | Hsp104∆N | hsp104-A201V | hsp104-A220T | hsp104-A22V | hsp104-A298V | hsp104-A341V | ... Show all

View all HSP104 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
Adenosine-binding protein chaperone involved protein folding, unfolding and refolding, cellular heat acclimation, and the inheritance of oxidatively modified proteins during replicative cell aging; localized to the nucleus and cytoplasm; subunit of the TRC endoplasmic reticulum (ER) membrane insertion complex

View computational annotations

Molecular Function

Manually Curated

Biological Process

Manually Curated

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.

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
Non-essential gene in reference strain S288C; null mutant shows decreased thermotolerance, shortened replicative lifespan, and increased loss of [PSI+] prion; overexpression slow growth and increased resistance to rapamycin

Classical Genetics

null
overexpression
reduction of function
activation
dominant negative

Large-scale Survey

null
overexpression
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
Hsp104p interacts physically with proteins involved in protein catabolism and transcription; HSP104 interacts genetically with genes involved in protein folding and chemical response

939 total interactions for 698 unique genes

Physical Interactions

  • Affinity Capture-MS: 740
  • Affinity Capture-RNA: 8
  • Affinity Capture-Western: 23
  • Biochemical Activity: 1
  • Co-crystal Structure: 6
  • Co-fractionation: 1
  • Co-localization: 10
  • Co-purification: 1
  • FRET: 1
  • PCA: 4
  • Protein-peptide: 4
  • Proximity Label-MS: 5
  • Reconstituted Complex: 27
  • Two-hybrid: 1

Genetic Interactions

  • Dosage Growth Defect: 3
  • Dosage Rescue: 15
  • Negative Genetic: 24
  • Phenotypic Enhancement: 15
  • Phenotypic Suppression: 29
  • Positive Genetic: 3
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 2
  • Synthetic Rescue: 10
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
HSP104 promoter is bound by Bur6p, Fkh2p, Gcn5p, Ncb2p, Rfx1p, Rgr1p, Spt6p, Spt7p, Srb5p, Sua7p, Tfc7p, Tup1p, and Xbp1p in response to heat; HSP104 transcription is regulated by Sfp1p in response to stress; HSP104 transcription is upregulated by Hsf1p in response to heat
Regulators
33
Targets
0
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: 2006-06-28

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
320
Additional
412
Reviews
203

Resources

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