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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-Experimental evidence at protein leveli

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

GO - Molecular functioni

  • chromatin DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • heat shock protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • promoter-specific chromatin binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein self-association Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl
  • RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • sequence-specific single stranded DNA binding Source: Ensembl
  • STAT family protein binding Source: Ensembl
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc
  • translation elongation factor binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-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.
SignaLinkiQ00613.
SIGNORiQ00613.

Names & Taxonomyi

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
Gene namesi
Name:HSF1Imported
Synonyms:HSTF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:5224. HSF1.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • condensed chromosome kinetochore Source: UniProtKB-SubCell
  • cytoplasm Source: UniProtKB
  • cytosol Source: HPA
  • euchromatin Source: Ensembl
  • heterochromatin Source: Ensembl
  • kinetochore Source: UniProtKB
  • mitotic spindle pole Source: UniProtKB
  • nuclear stress granule Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • PML body Source: UniProtKB
  • pronucleus Source: Ensembl
  • ribonucleoprotein complex Source: UniProtKB

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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

DisGeNETi3297.
OpenTargetsiENSG00000185122.
PharmGKBiPA29493.

Chemistry databases

ChEMBLiCHEMBL5869.

Polymorphism and mutation databases

BioMutaiHSF1.
DMDMi462333.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001245671 – 529Heat shock factor protein 1Add BLAST529

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei80N6-acetyllysine2 Publications1
Modified residuei91N6-acetyllysine; alternate1 Publication1
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

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

EPDiQ00613.
MaxQBiQ00613.
PaxDbiQ00613.
PeptideAtlasiQ00613.
PRIDEiQ00613.

PTM databases

iPTMnetiQ00613.
PhosphoSitePlusiQ00613.

Expressioni

Gene expression databases

BgeeiENSG00000185122.
CleanExiHS_HSF1.
ExpressionAtlasiQ00613. baseline and differential.
GenevisibleiQ00613. HS.

Organism-specific databases

HPAiCAB004239.
HPA008888.

Interactioni

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • heat shock protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • identical protein binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein self-association Source: UniProtKB
  • STAT family protein binding Source: Ensembl
  • translation elongation factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109530. 91 interactors.
DIPiDIP-35670N.
IntActiQ00613. 36 interactors.
MINTiMINT-230849.
STRINGi9606.ENSP00000431512.

Chemistry databases

BindingDBiQ00613.

Structurei

Secondary structure

1529
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi17 – 27Combined sources11
Helixi29 – 31Combined sources3
Turni32 – 34Combined sources3
Beta strandi35 – 37Combined sources3
Beta strandi39 – 42Combined sources4
Beta strandi44 – 47Combined sources4
Helixi49 – 55Combined sources7
Helixi57 – 60Combined sources4
Helixi66 – 75Combined sources10
Beta strandi79 – 83Combined sources5
Beta strandi87 – 91Combined sources5
Beta strandi96 – 100Combined sources5
Helixi109 – 114Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LDUNMR-A10-123[»]
5D5UX-ray2.91B1-120[»]
5D5VX-ray2.55B/D1-120[»]
5HDGX-ray1.70A15-120[»]
5HDNX-ray1.68A/B/C/D15-120[»]
ProteinModelPortaliQ00613.
SMRiQ00613.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
Motifi412 – 4209aaTAD1 Publication9

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

Sequence similaritiesi

Belongs to the HSF family.Curated

Phylogenomic databases

eggNOGiKOG0627. Eukaryota.
COG5169. LUCA.
GeneTreeiENSGT00390000001182.
HOGENOMiHOG000253917.
HOVERGENiHBG005999.
InParanoidiQ00613.
KOiK09414.
OMAiQFSLEHV.
OrthoDBiEOG091G087O.
PhylomeDBiQ00613.
TreeFamiTF330401.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR027072. HSF1.
IPR000232. HSF_DNA-bd.
IPR027725. HSF_fam.
IPR010542. Vert_HSTF_C.
IPR011991. WHTH_DNA-bd_dom.
PANTHERiPTHR10015. PTHR10015. 1 hit.
PTHR10015:SF211. PTHR10015:SF211. 1 hit.
PfamiView protein in Pfam
PF00447. HSF_DNA-bind. 1 hit.
PF06546. Vert_HS_TF. 1 hit.
PRINTSiPR00056. HSFDOMAIN.
SMARTiView protein in SMART
SM00415. HSF. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiView protein in PROSITE
PS00434. HSF_DOMAIN. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q00613-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDLPVGPGAA GPSNVPAFLT KLWTLVSDPD TDALICWSPS GNSFHVFDQG
60 70 80 90 100
QFAKEVLPKY FKHNNMASFV RQLNMYGFRK VVHIEQGGLV KPERDDTEFQ
110 120 130 140 150
HPCFLRGQEQ LLENIKRKVT SVSTLKSEDI KIRQDSVTKL LTDVQLMKGK
160 170 180 190 200
QECMDSKLLA MKHENEALWR EVASLRQKHA QQQKVVNKLI QFLISLVQSN
210 220 230 240 250
RILGVKRKIP LMLNDSGSAH SMPKYSRQFS LEHVHGSGPY SAPSPAYSSS
260 270 280 290 300
SLYAPDAVAS SGPIISDITE LAPASPMASP GGSIDERPLS SSPLVRVKEE
310 320 330 340 350
PPSPPQSPRV EEASPGRPSS VDTLLSPTAL IDSILRESEP APASVTALTD
360 370 380 390 400
ARGHTDTEGR PPSPPPTSTP EKCLSVACLD KNELSDHLDA MDSNLDNLQT
410 420 430 440 450
MLSSHGFSVD TSALLDLFSP SVTVPDMSLP DLDSSLASIQ ELLSPQEPPR
460 470 480 490 500
PPEAENSSPD SGKQLVHYTA QPLFLLDPGS VDTGSNDLPV LFELGEGSYF
510 520
SEGDGFAEDP TISLLTGSEP PKAKDPTVS
Length:529
Mass (Da):57,260
Last modified:February 1, 1994 - v1
Checksum:i735074507C954365
GO
Isoform Short (identifier: Q00613-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     462-489: GKQLVHYTAQPLFLLDPGSVDTGSNDLP → AGALHSAAAVPAGPRLRGHREQRPAGAV
     490-529: Missing.

Note: No experimental confirmation available.
Show »
Length:489
Mass (Da):52,881
Checksum:iFD6694B6D3927639
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002414462 – 489GKQLV…SNDLP → AGALHSAAAVPAGPRLRGHR EQRPAGAV in isoform Short. CuratedAdd BLAST28
Alternative sequenceiVSP_002415490 – 529Missing in isoform Short. CuratedAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64673 mRNA. Translation: AAA52695.1.
AK290975 mRNA. Translation: BAF83664.1.
BT007351 mRNA. Translation: AAP36015.1.
AC110280 Genomic DNA. No translation available.
AF205589 Genomic DNA. No translation available.
BC014638 mRNA. Translation: AAH14638.1.
CCDSiCCDS6419.1. [Q00613-1]
PIRiA41137.
RefSeqiNP_005517.1. NM_005526.3. [Q00613-1]
XP_016868866.1. XM_017013377.1. [Q00613-2]
UniGeneiHs.530227.

Genome annotation databases

EnsembliENST00000528838; ENSP00000431512; ENSG00000185122. [Q00613-1]
GeneIDi3297.
KEGGihsa:3297.
UCSCiuc003zbt.5. human. [Q00613-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiHSF1_HUMAN
AccessioniPrimary (citable) accession number: Q00613
Secondary accession number(s): A8K4L0, A8MW26, Q53XT4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: August 30, 2017
This is version 175 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families