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Entry version 194 (16 Oct 2019)
Sequence version 1 (01 Feb 1994)
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Protein

Heat shock factor protein 1

Gene

HSF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Function as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones heat shock proteins (HSPs) that protect cells from cellular insults' damage (PubMed:1871105, PubMed:11447121, PubMed:1986252, PubMed:7760831, PubMed:7623826, PubMed:8946918, PubMed:8940068, PubMed:9341107, PubMed:9121459, PubMed:9727490, PubMed:9499401, PubMed:9535852, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:25963659, PubMed:26754925). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:9727490, PubMed:11583998, PubMed:16278218). Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes (PubMed:1871105, PubMed:1986252, PubMed:8455624, PubMed:7935471, PubMed:7623826, PubMed:8940068, PubMed:9727490, PubMed:9499401, PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:25963659, PubMed:26754925). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock gene promoters (PubMed:25963659). Plays also several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells (PubMed:9341107). Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic progression (PubMed:18794143). Plays also a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner (PubMed:26359349). Involved in stress-induced cancer cell proliferation in a IER5-dependent manner (PubMed:26754925).27 Publications
(Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300.1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, DNA-binding
Biological processDNA damage, DNA repair, mRNA processing, mRNA transport, Stress response, Transcription, Transcription regulation, Transport

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-3371511 HSF1 activation
R-HSA-3371568 Attenuation phase
R-HSA-3371571 HSF1-dependent transactivation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q00613

SIGNOR Signaling Network Open Resource

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SIGNORi
Q00613

Protein family/group databases

MoonDB Database of extreme multifunctional and moonlighting proteins

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MoonDBi
Q00613 Predicted

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Heat shock factor protein 1Curated
Short name:
HSF 1
Alternative name(s):
Heat shock transcription factor 1Imported
Short name:
HSTF 1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HSF1Imported
Synonyms:HSTF1
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 8

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:5224 HSF1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
140580 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q00613

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi22L → A: Inhibits HSE DNA-binding activity and transcriptional activation. 1 Publication1
Mutagenesisi80K → Q: Loss of nuclear stress bodies localization. Loss of DNA-binding and transcriptional activities upon heat shock. No change in homotrimerization upon heat shock. 2 Publications1
Mutagenesisi80K → R: Does not change interaction with XRCC5 and XRCC6. Loss of nuclear stress bodies localization. Decreased nuclear stress bodies localization. Loss of DNA-binding and transcriptional activities upon heat shock. 3 Publications1
Mutagenesisi91K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi118K → Q: Loss of nuclear stress bodies localization. No change in protein abundance. 1 Publication1
Mutagenesisi118K → R: No change in nuclear stress bodies localization. 1 Publication1
Mutagenesisi120T → A: No effect on binding HSE nor on transcriptional activity. 1 Publication1
Mutagenesisi121S → A: Increased binding HSE and transcriptional activity. Greatly reduced binding to HSP90AA1. No effect on MAPKAPK2 binding. 1 Publication1
Mutagenesisi121S → D: Some inhibition of binding HSE and transcriptional activity. No change in binding HSP90AA1. Inhibits MAPKAPK2 binding. Decreased HSF1-induced expression of HSPA1A mRNA in a IER5-dependent manner; when associated with D-307; D-314; D-323 and D-367. 2 Publications1
Mutagenesisi123S → A: No effect on binding HSE nor on transcriptional activity. 1 Publication1
Mutagenesisi124T → A: No effect on binding HSE nor on transcriptional activity. 1 Publication1
Mutagenesisi126K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi140L → K: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Does not lead to constitutive transactivation activity at 20 degrees Celsius. Decreased DNA-binding activity at 37 degrees Celsius. 2 Publications1
Mutagenesisi142T → A: Reduced promoter activity by about 90%. Almost no transcriptional activity when coexpressed with CK2. 1 Publication1
Mutagenesisi147M → A: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Does not lead to constitutive transactivation activity at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 2 Publications1
Mutagenesisi147M → E: Does not lead to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Loss of DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi147M → K: Does not lead to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Loss of DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi150K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi162K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi189L → A: Does not lead to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Leads to constitutive homotrimerization and DNA-binding activities at 30 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi189L → E: Leads to constitutive homotrimerization, DNA-binding and transactivation activities at 20 degrees Celsius. Decreased DNA-binding activity at 37 degrees Celsius. 2 Publications1
Mutagenesisi189L → K: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi193L → A: Does not lead to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Leads to constitutive homotrimerization and DNA-binding activities at 30 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi193L → E: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Decreased DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi193L → K: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Loss of DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi208K → Q: No change in nuclear stress bodies localization. Increased protein abundance. 1 Publication1
Mutagenesisi208K → R: No change in nuclear stress bodies localization. No change in protein abundance. 1 Publication1
Mutagenesisi216S → A: Does not change interaction with XRCC5 and XRCC6. No PLK1-induced phosphorylation in mitosis. Inhibits PLK1-stimulated ubiquitinylation. Increased protein stability. 2 Publications1
Mutagenesisi216S → E: Does not change interaction with XRCC5 and XRCC6. No change in spindle pole localization. Increases weakly PLK1-stimulated ubiquitinylation. No change in protein stability. Increased interaction with BTRC. 2 Publications1
Mutagenesisi216S → N: Decreased spindle pole localization. Decreased interaction with BTRC. Increased protein stability. 1 Publication1
Mutagenesisi230S → A: No phosphorylation. No change in PLK1-induced phosphorylation in mitosis. No change in DNA-binding activity upon heat shock. Decreased transcriptional activity upon heat shock. 3 Publications1
Mutagenesisi230S → D: Mimics phosphorylation. No effect on transcriptional activity upon heat shock. 2 Publications1
Mutagenesisi275S → A: Reduced increase in heat-induced transcriptional activity. 1 Publication1
Mutagenesisi275S → G: Leads to weak constitutive transactivation activity at room temperature. 1 Publication1
Mutagenesisi292S → A: Weak decreased PLK1-induced phosphorylation. Increased nuclear localization upon heat shock. 1 Publication1
Mutagenesisi296R → A: No effect neither on repression of transcriptional activity at control temperature nor on transcriptional activation upon heat shock. 1 Publication1
Mutagenesisi297V → A: Slight effect on derepression of transcriptional activity at control temperature and on transcriptional activation upon heat shock. 1 Publication1
Mutagenesisi298K → A: Induces derepression of transcriptional activity at control temperature. 2 Publications1
Mutagenesisi298K → Q: No change in nuclear stress bodies localization. Increased protein abundance. 1 Publication1
Mutagenesisi298K → R: Abolishes sumoylation. No effect on phosphorylation of S-303 nor of S-307. No change in subcellular location to nuclear stress granules upon heat shock. Loss of colocalization with SUMO1 to nuclear stress granules upon heat shock. Does not change interaction with XRCC5 and XRCC6. No effect on binding to HSE nor on transactivation of HSP70. Increases transcriptional activity in a DAXX-dependent manner. No change in protein abundance. 7 Publications1
Mutagenesisi299E → A: No effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi300E → A: Induces derepression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi303S → A: No phosphorylation nor sumoylation. No change in nuclear stress granules subcellular location upon heat shock. Loss of colocalization with SUMO1 to nuclear stress granules upon heat shock. Slight decrease in transcriptional activity on heat treatment. No change in PLK1-induced phosphorylation in mitosis, induces derepression of transcription activation at control temperature, abolishes sumoylation and induces 2.5-fold increase in transcriptional activity on heat treatment; when associated with A-307. 6 Publications1
Mutagenesisi303S → D: Mimics phosphorylation. No effect on in vitro sumoylation. Greatly increased transcriptional activity on heat induction. 5-fold derepression of transcriptional activity at control temperature; when associated with D-307. 4 Publications1
Mutagenesisi303S → G: Leads to constitutive transactivation activity at room temperature. Inhibits interaction with YWHAE and increases cytoplasmic localization; when associated with G-307. 2 Publications1
Mutagenesisi307S → A: No phosphorylation. Does not reduce Ser-303 phosphorylation. 1.5% increase in transcriptional activity on heat-treatment. No change in PLK1-induced phosphorylation in mitosis, induces derepression of transcription activation at control temperature, abolishes sumoylation and induces 2.5-fold increase in transcriptional activity on heat treatment; when associated with A-303. 6 Publications1
Mutagenesisi307S → D: 5-fold derepression of transcriptional activity at control temperature; when associated with D-303. Decreased HSF1-induced expression of HSPA1A mRNA in a IER5-dependent manner; when associated with D-121; D-314; D-323 and D-367. 3 Publications1
Mutagenesisi307S → G: Leads to constitutive transactivation activity at room temperature. Inhibits interaction with YWHAE and increases cytoplasmic localization; when associated with G-303. 2 Publications1
Mutagenesisi309R → A: No effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi311E → A: No effect neither on repression of transcriptional activity at control temperature nor on transcriptional activation upon heat shock. 1 Publication1
Mutagenesisi314S → A: Weak decreased PLK1-induced phosphorylation. 1 Publication1
Mutagenesisi314S → D: Decreased HSF1-induced expression of HSPA1A mRNA in a IER5-dependent manner; when associated with D-121; D-307; D-323 and D-367. 1 Publication1
Mutagenesisi319S → A: Weak decreased PLK1-induced phosphorylation. 1 Publication1
Mutagenesisi320S → A: Decreased nuclear localization and transcriptional activity upon heat shock. 1 Publication1
Mutagenesisi320S → D: Increased nuclear localization and transcriptional activity upon heat shock. 1 Publication1
Mutagenesisi323T → D: Decreased HSF1-induced expression of HSPA1A mRNA in a IER5-dependent manner; when associated with D-121; D-307; D-314 and D-367. 1 Publication1
Mutagenesisi326S → A: No phosphorylation. Increased nuclear localization upon heat shock. No effect on oligomerization, DNA-binding activities and nuclear localization. Significant decrease in transcriptional activity by heat shock. Decreases transcriptional activity in a DAXX-dependent manner. Does not change interaction with XRCC5 and XRCC6. Weak decreased PLK1-induced phosphorylation. 5 Publications1
Mutagenesisi326S → E: Does not change interaction with XRCC5 and XRCC6. 1 Publication1
Mutagenesisi363S → A: Decreases MAPK8-induced phosphorylation and does not negatively regulates transactivating activity upon heat shock. No effect on sumoylation. 2 Publications1
Mutagenesisi367T → D: Decreased HSF1-induced expression of HSPA1A mRNA in a IER5-dependent manner; when associated with D-121; D-307; D-314 and D-323. 1 Publication1
Mutagenesisi381K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi391M → A: Does not lead to constitutive DNA-binding activity at 20 degrees Celsius. Leads to weak constitutive DNA-binding and homotrimerization activities at 30 degrees Celsius. Decreased DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi391M → E: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. Does not lead to constitutive transactivation activity at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 2 Publications1
Mutagenesisi391M → K: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi395L → E: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi395L → K: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius. 1 Publication1
Mutagenesisi419S → A: Does not change interaction with XRCC5 and XRCC6. Decreased nuclear localization upon heat shock. Strongly decreases PLK1-induced phosphorylation. No change in PLK1-induced phosphorylation in mitosis. 3 Publications1
Mutagenesisi419S → E: Does not change interaction with XRCC5 and XRCC6. 1 Publication1
Mutagenesisi527T → A: No change in binding HSE nor on transcriptional activity. Decreased binding HSE; when associated with A-529. 1 Publication1
Mutagenesisi529S → A: No change in binding HSE nor on transcriptional activity. Decreased binding HSE; when associated with A-527. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
3297

Open Targets

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OpenTargetsi
ENSG00000185122

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA29493

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
Q00613

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL5869

Drug and drug target database

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DrugBanki
DB06258 Bimoclomol

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
HSF1

Domain mapping of disease mutations (DMDM)

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DMDMi
462333

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001245671 – 529Heat shock factor protein 1Add BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1N-acetylmethionineCombined sources1
Modified residuei80N6-acetyllysine2 Publications1
Modified residuei91N6-acetyllysine; alternate1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki91Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei118N6-acetyllysine2 Publications1
Modified residuei121Phosphoserine; by MAPKAPK22 Publications1
Cross-linki126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki131Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei142Phosphothreonine; by CK21 Publication1
Modified residuei150N6-acetyllysine1 Publication1
Modified residuei188N6-acetyllysine1 Publication1
Modified residuei208N6-acetyllysine; alternate1 Publication1
Cross-linki208Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei216Phosphoserine; by PLK11 Publication1
Cross-linki224Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei230Phosphoserine; by CAMK2A2 Publications1
Modified residuei275Phosphoserine1 Publication1
Modified residuei292Phosphoserine1 Publication1
Modified residuei298N6-acetyllysine; alternate1 Publication1
Cross-linki298Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate3 Publications
Cross-linki298Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei303Phosphoserine; by GSK3-betaCombined sources7 Publications1
Modified residuei307Phosphoserine; by MAPK3Combined sources6 Publications1
Modified residuei314PhosphoserineCombined sources1 Publication1
Modified residuei319Phosphoserine1 Publication1
Modified residuei320Phosphoserine; by PKA2 Publications1
Modified residuei323PhosphothreonineCombined sources1
Modified residuei326Phosphoserine; by MAPK12Combined sources2 Publications1
Modified residuei344Phosphoserine1 Publication1
Modified residuei363Phosphoserine; by MAPK8Combined sources2 Publications1
Modified residuei419Phosphoserine; by PLK11 Publication1
Modified residuei444Phosphoserine1 Publication1
Modified residuei524N6-acetyllysine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated (PubMed:9499401, PubMed:10359787, PubMed:11583998, PubMed:26159920). Phosphorylated in unstressed cells; this phosphorylation is constitutive and implicated in the repression of HSF1 transcriptional activity (PubMed:8946918, PubMed:8940068, PubMed:9121459, PubMed:16278218). Phosphorylated on Ser-121 by MAPKAPK2; this phosphorylation promotes interaction with HSP90 proteins and inhibits HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Phosphorylation on Ser-303 by GSK3B/GSK3-beta and on Ser-307 by MAPK3 within the regulatory domain is involved in the repression of HSF1 transcriptional activity and occurs in a RAF1-dependent manner (PubMed:8946918, PubMed:8940068, PubMed:9121459, PubMed:9535852, PubMed:10747973, PubMed:12646186). Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner (PubMed:12917326). Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303 (PubMed:8940068). According to PubMed:9535852, Ser-303 is not phosphorylated in unstressed cells. Phosphorylated on Ser-419 by PLK1; phosphorylation promotes nuclear translocation upon heat shock (PubMed:15661742). Hyperphosphorylated upon heat shock and during the attenuation and recovery phase period of the heat shock response (PubMed:11447121, PubMed:12659875, PubMed:24581496). Phosphorylated on Thr-142; this phosphorylation increases HSF1 transactivation activity upon heat shock (PubMed:12659875). Phosphorylation on Ser-230 by CAMK2A; this phosphorylation enhances HSF1 transactivation activity upon heat shock (PubMed:11447121). Phosphorylation on Ser-326 by MAPK12; this phosphorylation enhances HSF1 nuclear translocation, homotrimerization and transactivation activities upon heat shock (PubMed:15760475, PubMed:27354066). Phosphorylated on Ser-320 by PRKACA/PKA; this phosphorylation promotes nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Phosphorylated on Ser-363 by MAPK8; this phosphorylation occurs upon heat shock, induces HSF1 translocation into nuclear stress bodies and negatively regulates transactivation activity (PubMed:10747973). Neither basal nor stress-inducible phosphorylation on Ser-230, Ser-292, Ser-303, Ser-307, Ser-314, Ser-319, Ser-320, Thr-323, Ser-326, Ser-338, Ser-344, Ser-363, Thr-367, Ser-368 and Thr-369 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity (PubMed:25963659). Phosphorylated on Ser-216 by PLK1 in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex inducing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Dephosphorylated on Ser-121, Ser-307, Ser-314, Thr-323 and Thr-367 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity (PubMed:26754925).21 Publications
Sumoylated with SUMO1 and SUMO2 upon heat shock in a ERK2-dependent manner (PubMed:12646186, PubMed:12665592). Sumoylated by SUMO1 on Lys-298; sumoylation occurs upon heat shock and promotes its localization to nuclear stress bodies and DNA-binding activity (PubMed:11514557). Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation (PubMed:12646186, PubMed:12665592).3 Publications
Acetylated on Lys-118; this acetylation is decreased in a IER5-dependent manner (PubMed:26754925). Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner (PubMed:24581496, PubMed:27189267). Acetylated on Lys-80; this acetylation inhibits DNA-binding activity upon heat shock (PubMed:19229036). Deacetylated on Lys-80 by SIRT1; this deacetylation increases DNA-binding activity (PubMed:19229036).4 Publications
Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis (PubMed:18794143). Polyubiquitinated (PubMed:24581496). Undergoes proteasomal degradation upon heat shock and during the attenuation and recovery phase period of the heat shock response (PubMed:24581496).2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q00613

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q00613

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
Q00613

MaxQB - The MaxQuant DataBase

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MaxQBi
Q00613

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q00613

PeptideAtlas

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PeptideAtlasi
Q00613

PRoteomics IDEntifications database

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PRIDEi
Q00613

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
57864 [Q00613-1]
57865 [Q00613-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q00613

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q00613

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000185122 Expressed in 170 organ(s), highest expression level in testis

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q00613 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q00613 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB004239
HPA008888

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer; cytoplasmic latent and transcriptionally inactive monomeric form in unstressed cells (PubMed:8455624, PubMed:7935376, PubMed:7935471, PubMed:7623826, PubMed:9222587, PubMed:9727490, PubMed:11583998). Homotrimer; in response to stress, such as heat shock, homotrimerizes and translocates into the nucleus, binds to heat shock element (HSE) sequences in promoter of heat shock protein (HSP) genes and acquires transcriptional ability (PubMed:8455624, PubMed:7935471, PubMed:7623826, PubMed:9222587, PubMed:9727490, PubMed:11583998, PubMed:26754925, PubMed:26727489).

Interacts (via monomeric form) with FKBP4; this interaction occurs in unstressed cells (PubMed:11583998). Associates (via monomeric form) with HSP90 proteins in a multichaperone complex in unnstressed cell; this association maintains HSF1 in a non-DNA-binding and transcriptional inactive form by preventing HSF1 homotrimerization (PubMed:9727490, PubMed:11583998, PubMed:15661742, PubMed:16278218). Homotrimeric transactivation activity is modulated by protein-protein interactions and post-translational modifications (PubMed:11583998, PubMed:15016915, PubMed:16554823, PubMed:26754925).

Interacts with HSP90AA1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (PubMed:26754925). Part (via regulatory domain in the homotrimeric form) of a large heat shock-induced HSP90-dependent multichaperone complex at least composed of FKBP4, FKBP5, HSP90 proteins, PPID, PPP5C and PTGES3; this association maintains the HSF1 homotrimeric DNA-bound form in a transcriptionally inactive form (PubMed:9727490, PubMed:11583998, PubMed:16278218).

Interacts with BAG3 (via BAG domain); this interaction occurs in normal and heat-shocked cells promoting nuclear shuttling of HSF1 in a BAG3-dependent manner (PubMed:26159920).

Interacts (via homotrimeric and hyperphosphorylated form) with FKBP4; this interaction occurs upon heat shock in a HSP90-dependent multichaperone complex (PubMed:11583998).

Interacts (via homotrimeric form preferentially) with EEF1A proteins (PubMed:15016915). In heat shocked cells, stress-denatured proteins compete with HSF1 homotrimeric DNA-bound form for association of the HSP90-dependent multichaperone complex, and hence alleviating repression of HSF1-mediated transcriptional activity (PubMed:11583998).

Interacts (via homotrimeric form preferentially) with DAXX; this interaction relieves homotrimeric HSF1 from repression of its transcriptional activity by HSP90-dependent multichaperone complex upon heat shock (PubMed:15016915).

Interacts (via D domain and preferentially with hyperphosphorylated form) with JNK1; this interaction occurs under both normal growth conditions and immediately upon heat shock (PubMed:10747973).

Interacts (via D domain and preferentially with hyperphosphorylated form) with MAPK3; this interaction occurs upon heat shock (PubMed:10747973).

Interacts with IER5 (via central region); this interaction promotes PPP2CA-induced dephosphorylation on Ser-121, Ser-307, Ser-314, Thr-323 and Thr-367 and HSF1 transactivation activity (PubMed:25816751, PubMed:26496226, PubMed:26754925).

Found in a ribonucleoprotein complex composed of the HSF1 homotrimeric form, translation elongation factor eEF1A proteins and non-coding RNA heat shock RNA-1 (HSR1); this complex occurs upon heat shock and stimulates HSF1 DNA-binding activity (PubMed:16554823).

Interacts (via transactivation domain) with HSPA1A/HSP70 and DNAJB1; these interactions result in the inhibition of heat shock- and HSF1-induced transcriptional activity during the attenuation and recovery phase from heat shock (PubMed:7935376, PubMed:9222587, PubMed:9499401).

Interacts (via Ser-303 and Ser-307 phosphorylated form) with YWHAE; this interaction promotes HSF1 sequestration in the cytoplasm in an ERK-dependent manner (PubMed:12917326).

Found in a complex with IER5 and PPP2CA (PubMed:26754925).

Interacts with TPR; this interaction increases upon heat shock and stimulates export of HSP70 mRNA (PubMed:17897941).

Interacts with SYMPK (via N-terminus) and CSTF2; these interactions occur upon heat shock (PubMed:14707147).

Interacts (via transactivation domain) with HSPA8 (PubMed:9499401).

Interacts with EEF1D; this interaction occurs at heat shock promoter element (HSE) sequences (PubMed:21597468).

Interacts with MAPKAPK2 (PubMed:16278218).

Interacts with PRKACA/PKA (PubMed:21085490).

Interacts (via transactivation domain) with GTF2A2 (PubMed:11005381).

Interacts (via transactivation domain) with GTF2B (PubMed:11005381).

Interacts (via transactivation domain) with TBP (PubMed:11005381).

Interacts with CDK9, CCNT1 and EP300 (PubMed:27189267).

Interacts (via N-terminus) with XRCC5 (via N-terminus) and XRCC6 (via N-terminus); these interactions are direct and prevent XRCC5/XRCC6 heterodimeric binding and non-homologous end joining (NHEJ) repair activities induced by ionizing radiation (IR) (PubMed:26359349).

Interacts with PLK1; this interaction occurs during the early mitotic period, increases upon heat shock but does not modulate neither HSF1 homotrimerization and DNA-binding activities (PubMed:15661742, PubMed:18794143).

Interacts (via Ser-216 phosphorylated form) with CDC20; this interaction occurs in mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated degradation of HSF1 by blocking the recruitment of the SCF(BTRC) ubiquitin ligase complex (PubMed:18794143).

Interacts with MAD2L1; this interaction occurs in mitosis (PubMed:18794143).

Interacts with BTRC; this interaction occurs during mitosis, induces its ubiquitin-dependent degradation following stimulus-dependent phosphorylation at Ser-216, a process inhibited by CDC20 (PubMed:18794143).

Interacts with HSP90AA1 and HSP90AB1 (PubMed:26517842).

1 Publication28 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
109530, 117 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q00613

Database of interacting proteins

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DIPi
DIP-35670N

Protein interaction database and analysis system

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IntActi
Q00613, 42 interactors

Molecular INTeraction database

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MINTi
Q00613

STRING: functional protein association networks

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STRINGi
9606.ENSP00000431512

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q00613

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1529
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q00613

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni15 – 120DNA-binding domain2 PublicationsAdd BLAST106
Regioni130 – 203Hydrophobic repeat HR-A/B1 PublicationAdd BLAST74
Regioni203 – 224D domain1 PublicationAdd BLAST22
Regioni221 – 310Regulatory domain1 PublicationAdd BLAST90
Regioni371 – 529Transactivation domain2 PublicationsAdd BLAST159
Regioni384 – 409Hydrophobic repeat HR-C1 PublicationAdd BLAST26

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi412 – 4209aaTAD1 Publication9

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

In unstressed cells, spontaneous homotrimerization is inhibited (PubMed:7935471, PubMed:7760831). Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation (PubMed:7935471, PubMed:7623826). Furthermore, intramolecular interactions between the regulatory domain and the nonadjacent transactivation domain prevents transcriptional activation, a process that is relieved upon heat shock (PubMed:7760831). The regulatory domain is necessary for full repression of the transcriptional activation domain in unstressed cells through its phosphorylation on Ser-303 and Ser-307 (PubMed:8946918, PubMed:9121459). In heat stressed cells, HSF1 homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity (PubMed:7935471). The D domain is necessary for translocation to the nucleus, interaction with JNK1 and MAPK3 and efficient JNK1- and MAPK3-dependent phosphorylation (PubMed:10747973). The regulatory domain confers heat shock inducibility on the transcriptional transactivation domain (PubMed:7760831). The regulatory domain is necessary for transcriptional activation through its phosphorylation on Ser-230 upon heat shock (PubMed:11447121). 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors (PubMed:17467953).8 Publications

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the HSF family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0627 Eukaryota
COG5169 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158421

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000253917

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q00613

KEGG Orthology (KO)

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KOi
K09414

Identification of Orthologs from Complete Genome Data

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OMAi
LICWSPQ

Database of Orthologous Groups

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OrthoDBi
1154048at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q00613

TreeFam database of animal gene trees

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TreeFami
TF330401

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR000232 HSF_DNA-bd
IPR027725 HSF_fam
IPR010542 Vert_HSTF_C
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf

The PANTHER Classification System

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PANTHERi
PTHR10015 PTHR10015, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00447 HSF_DNA-bind, 1 hit
PF06546 Vert_HS_TF, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00056 HSFDOMAIN

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00415 HSF, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF46785 SSF46785, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00434 HSF_DOMAIN, 1 hit