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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

DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. In higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked.8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi15 – 120By similarityAdd BLAST106

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Stress response, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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 1
Short name:
HSF 1
Alternative name(s):
Heat shock transcription factor 1
Short name:
HSTF 1
Gene namesi
Name:HSF1
Synonyms:HSTF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:5224. HSF1.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Cytoplasmic during normal growth. On activation, translocates to nuclear stress granules. Colocalizes with SUMO1 in nuclear stress granules.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • euchromatin Source: Ensembl
  • heterochromatin Source: Ensembl
  • nuclear stress granule Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
  • pronucleus Source: Ensembl
  • protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91K → R: No effect on sumoylation. 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. 1 Publication1
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
Mutagenesisi142T → A: Reduced promoter activity by about 90%. Almost no transcriptional activity when coexpressed with CK2. 1 Publication1
Mutagenesisi150K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi162K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi230S → A: No phosphorylation. Impaired transcriptional activity. No change in inducible DNA-binding activity. 2 Publications1
Mutagenesisi230S → D: Mimics phosphorylation. No effect on transcriptional activity. 2 Publications1
Mutagenesisi275S → A: Reduced increase in heat-induced transcriptional activity. 1 Publication1
Mutagenesisi296R → A: No effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi297V → A: Slight effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi298K → A: Derepression of transcriptional activity at control temperature by 18.5%. 3 Publications1
Mutagenesisi298K → R: Abolishes sumoylation. No effect on phosphorylation of S-303 nor of S-307. No effect on binding to HSE nor on transactivation of HSP70. 3 Publications1
Mutagenesisi299E → A: No effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi300E → A: Derepression of transcriptional activity at control temperature by 11%. 1 Publication1
Mutagenesisi303S → A: No phosphorylation nor sumoylation. No change in subcellular location to nuclear stress granules. Slight decrease in transcriptional activity on heat treatment. 2.5-fold increase in transcriptional activity on heat treatment; when associated with A-303. 4 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 A-307. 4 Publications1
Mutagenesisi307S → A: No phosphorylation. 5-fold derepression of transcriptional activity at control temperature; when associated with A-303. 1.5% increase in transcriptional activity on heat-treatment. 2.5-fold increase in transcriptional activity on heat treatment; when associated with A-303. 4 Publications1
Mutagenesisi309R → A: No effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi311E → A: No effect on repression of transcriptional activity at control temperature. 1 Publication1
Mutagenesisi326S → A: No phosphorylation. Significant decrease in transcriptional activity by heat stress. 1 Publication1
Mutagenesisi363S → A: No effect on sumoylation. 1 Publication1
Mutagenesisi381K → R: No effect on sumoylation. 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 residuei121Phosphoserine; by MAPKAPK22 Publications1
Modified residuei142Phosphothreonine; by CK21 Publication1
Modified residuei230Phosphoserine2 Publications1
Modified residuei292Phosphoserine1 Publication1
Cross-linki298Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)3 Publications
Modified residuei303PhosphoserineCombined sources6 Publications1
Modified residuei307PhosphoserineCombined sources5 Publications1
Modified residuei314PhosphoserineCombined sources1 Publication1
Modified residuei323PhosphothreonineCombined sources1
Modified residuei326PhosphoserineCombined sources1 Publication1
Modified residuei344Phosphoserine1 Publication1
Modified residuei363PhosphoserineCombined sources1 Publication1
Modified residuei419Phosphoserine1 Publication1
Modified residuei444Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated on multiple serine residues, a subset of which are involved in stress-related regulation of transcription activation. Constitutive phosphorylation represses transcriptional activity at normal temperatures. Levels increase on specific residues heat-shock and enhance HSF1 transactivation activity. Phosphorylation on Ser-307 derepresses activation on heat-stress and in combination with Ser-303 phosphorylation appears to be involved in recovery after heat-stress. Phosphorylated on Ser-230 by CAMK2, in vitro. Cadmium also enhances phosphorylation at this site. Phosphorylation on Ser-303 is a prerequisite for HSF1 sumoylation. Phosphorylation on Ser-121 inhibits transactivation and promotes HSP90 binding. Phosphorylation on Thr-142 also mediates transcriptional activity induced by heat. Phosphorylation on Ser-326 plays an important role in heat activation of HSF1 transcriptional activity.9 Publications
Sumoylated with SUMO1 and SUMO2 on heat-shock. Heat-inducible sumoylation occurs after 15 min of heat-shock, after which levels decrease and at 4 hours, levels return to control levels. Sumoylation has no effect on HSE binding nor on transcriptional activity. Phosphorylation on Ser-303 is a prerequisite for sumoylation.6 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. Under normal conditions, interacts with HSP90AA1 in the HSP90 multichaperone complex; the interaction prevents trimerization and activation of HSF1. On activation by heat-stress or by other factors such as metal ions, HSF1 is released from the complex, homotrimerizes, is hyperphosphorylated and translocated to the nucleus where, subsequently, it can activate transcription. Binds the complex through the regulatory domain. Interacts with SYMPK and CSTF2 in heat-stressed cells. Interacts with FKBP4 in the HSP90 multichaperone complex; the interaction is independent of the phosphorylation state of HSF1. Interacts with MAPKAPK2. Interacts with EEF1D at heat shock promoter elements (HSE).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IER5Q5VY093EBI-719620,EBI-1774000
MAPKAPK2P491375EBI-719620,EBI-993299
MINK1Q8N4C82EBI-719620,EBI-2133481
PRKCQQ047592EBI-719620,EBI-374762

GO - Molecular functioni

  • heat shock protein binding Source: UniProtKB
  • identical protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109530. 88 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 strandi41 – 47Combined sources7
Helixi49 – 55Combined sources7
Helixi57 – 60Combined sources4
Helixi66 – 75Combined sources10
Beta strandi79 – 81Combined sources3
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[»]
ProteinModelPortaliQ00613.
SMRiQ00613.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 203Hydrophobic repeat HR-A/BAdd BLAST74
Regioni221 – 310Regulatory domainAdd BLAST90
Regioni371 – 529Transactivation domainAdd BLAST159
Regioni384 – 409Hydrophobic repeat HR-CAdd BLAST26

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi412 – 4209aaTAD9

Domaini

the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.2 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.
InterProiIPR027072. HSF1.
IPR000232. HSF_DNA-bd.
IPR027725. HSF_fam.
IPR010542. Vert_HSTF_C.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR10015. PTHR10015. 2 hits.
PTHR10015:SF182. PTHR10015:SF182. 2 hits.
PfamiPF00447. HSF_DNA-bind. 1 hit.
PF06546. Vert_HS_TF. 1 hit.
[Graphical view]
PRINTSiPR00056. HSFDOMAIN.
SMARTiSM00415. HSF. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00434. HSF_DOMAIN. 1 hit.
[Graphical view]

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

Cross-referencesi

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.

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[»]
ProteinModelPortaliQ00613.
SMRiQ00613.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109530. 88 interactors.
DIPiDIP-35670N.
IntActiQ00613. 36 interactors.
MINTiMINT-230849.
STRINGi9606.ENSP00000431512.

Chemistry databases

BindingDBiQ00613.
ChEMBLiCHEMBL5869.

PTM databases

iPTMnetiQ00613.
PhosphoSitePlusiQ00613.

Polymorphism and mutation databases

BioMutaiHSF1.
DMDMi462333.

Proteomic databases

EPDiQ00613.
MaxQBiQ00613.
PaxDbiQ00613.
PeptideAtlasiQ00613.
PRIDEiQ00613.

Protocols and materials databases

DNASUi3297.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3297.
DisGeNETi3297.
GeneCardsiHSF1.
HGNCiHGNC:5224. HSF1.
HPAiCAB004239.
HPA008888.
MIMi140580. gene.
neXtProtiNX_Q00613.
OpenTargetsiENSG00000185122.
PharmGKBiPA29493.
GenAtlasiSearch...

Phylogenomic databases

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

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.

Miscellaneous databases

ChiTaRSiHSF1. human.
GeneWikiiHSF1.
GenomeRNAii3297.
PROiQ00613.
SOURCEiSearch...

Gene expression databases

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

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR027072. HSF1.
IPR000232. HSF_DNA-bd.
IPR027725. HSF_fam.
IPR010542. Vert_HSTF_C.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERiPTHR10015. PTHR10015. 2 hits.
PTHR10015:SF182. PTHR10015:SF182. 2 hits.
PfamiPF00447. HSF_DNA-bind. 1 hit.
PF06546. Vert_HS_TF. 1 hit.
[Graphical view]
PRINTSiPR00056. HSFDOMAIN.
SMARTiSM00415. HSF. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00434. HSF_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHSF1_HUMAN
AccessioniPrimary (citable) accession number: Q00613
Secondary accession number(s): A8K4L0, A8MW26, Q53XT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: November 30, 2016
This is version 167 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.