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Heat shock factor protein 1



Mus musculus (Mouse)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. 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. Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. 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. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner. Plays a role in nuclear export of stress-induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Plays also a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner.By similarity

GO - Molecular functioni

GO - Biological processi


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

Enzyme and pathway databases

ReactomeiR-MMU-3371453. Regulation of HSF1-mediated heat shock response.
R-MMU-3371511. HSF1 activation.
R-MMU-3371568. Attenuation phase.
R-MMU-3371571. HSF1-dependent transactivation.

Names & Taxonomyi

Protein namesi
Recommended name:
Heat shock factor protein 1By similarity
Short name:
Alternative name(s):
Heat shock transcription factor 1By similarity
Short name:
Gene namesi
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:96238. Hsf1.

Subcellular locationi

  • Nucleus 1 Publication
  • Cytoplasm 1 Publication
  • Nucleusnucleoplasm By similarity
  • Cytoplasmperinuclear region By similarity
  • Cytoplasmcytoskeletonspindle pole By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
  • Chromosomecentromerekinetochore By similarity

  • Note: The monomeric form is cytoplasmic in unstressed cells (PubMed:26159920). Predominantly nuclear protein in both unstressed and heat shocked cells. Translocates in the nucleus upon heat shock. Nucleocytoplasmic shuttling protein. Colocalizes with IER5 in the nucleus. Colocalizes with BAG3 to the nucleus upon heat stress. Localizes in subnuclear granules called nuclear stress bodies (nSBs) upon heat shock. Colocalizes with SYMPK and SUMO1 in nSBs upon heat shock. Colocalizes with PRKACA/PKA in the nucleus and nSBs upon heat shock. Relocalizes from the nucleus to the cytoplasm during the attenuation and recovery phase period of the heat shock response. Translocates in the cytoplasm in a YWHAE- and XPO1/CRM1-dependent manner. Together with histone H2AX, redistributed in discrete nuclear DNA damage-induced foci after ionizing radiation (IR). Colocalizes with calcium-responsive transactivator SS18L1 at kinetochore region on the mitotic chromosomes. Colocalizes with gamma tubulin at centrosome. Localizes at spindle pole in metaphase. Colocalizes with PLK1 at spindle poles during prometaphase.By similarity1 Publication

GO - Cellular componenti

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

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Nucleus

Pathology & Biotechi

Chemistry databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001245681 – 525Heat shock factor protein 1Add BLAST525

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei80N6-acetyllysineBy similarity1
Modified residuei91N6-acetyllysineBy similarity1
Modified residuei118N6-acetyllysineBy similarity1
Modified residuei121Phosphoserine; by MAPKAPK2By similarity1
Modified residuei142Phosphothreonine; by CK2By similarity1
Modified residuei150N6-acetyllysineBy similarity1
Modified residuei188N6-acetyllysineBy similarity1
Modified residuei208N6-acetyllysineBy similarity1
Modified residuei216Phosphoserine; by PLK1By similarity1
Modified residuei230Phosphoserine; by CAMK2ABy similarity1
Modified residuei275PhosphoserineBy similarity1
Modified residuei292PhosphoserineBy similarity1
Modified residuei298N6-acetyllysineBy similarity1
Cross-linki298Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei303Phosphoserine; by GSK3-betaCombined sourcesBy similarity1
Modified residuei307Phosphoserine; by MAPK3Combined sourcesBy similarity1
Modified residuei314PhosphoserineBy similarity1
Modified residuei319PhosphoserineBy similarity1
Modified residuei320Phosphoserine; by PKABy similarity1
Modified residuei323PhosphothreonineBy similarity1
Modified residuei326Phosphoserine; by MAPK12By similarity1
Modified residuei345PhosphoserineBy similarity1
Modified residuei415Phosphoserine; by PLK1By similarity1
Modified residuei440PhosphoserineBy similarity1
Modified residuei520N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylated in unstressed cells; this phosphorylation is constitutive and implicated in the repression of HSF1 transcriptional activity. Phosphorylated on Ser-121 by MAPKAPK2; this phosphorylation promotes interaction with HSP90 proteins and inhibits HSF1 homotrimerization, DNA-binding and transactivation activities. Phosphorylation on Ser-303 by GSK3B/GSK3-beat 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. Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner. Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303. According to, Ser-303 is not phosphorylated in unstressed cells. Phosphorylated on Ser-415 by PLK1; phosphorylation promotes nuclear translocation upon heat shock. Hyperphosphorylated upon heat shock and during the attenuation and recovery phase period of the heat shock response. Phosphorylated on Thr-142; this phosphorylation increases HSF1 transactivation activity upon heat shock. Phosphorylation on Ser-230 by CAMK2A; this phosphorylation enhances HSF1 transactivation activity upon heat shock. Phosphorylation on Ser-326 by MAPK12; this phosphorylation enhances HSF1 nuclear translocation, homotrimerization and transactivation activities upon heat shock. Phosphorylated on Ser-320 by PRKACA/PKA; this phosphorylation promotes nuclear localization and transcriptional activity upon heat shock. Phosphorylated by MAPK8; this phosphorylation occurs upon heat shock, induces HSF1 translocation into nuclear stress bodies and negatively regulates transactivation activity. 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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity. 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. Dephosphorylated on Ser-121, Ser-307, Ser-314 and Thr-323 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity.By similarity
Sumoylated with SUMO1 and SUMO2 upon heat shock in a ERK2-dependent manner. Sumoylated by SUMO1 on Lys-298; sumoylation occurs upon heat shock and promotes its localization to nuclear stress bodies and DNA-binding activity. Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.By similarity
Acetylated on Lys-118; this acetylation is decreased in a IER5-dependent manner. Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner. Acetylated on Lys-80; this acetylation inhibits DNA-binding activity upon heat shock. Deacetylated on Lys-80 by SIRT1; this deacetylation increases DNA-binding activity.By similarity
Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis. Polyubiquitinated. Undergoes proteasomal degradation upon heat shock and during the attenuation and recovery phase period of the heat shock response.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Gene expression databases

ExpressionAtlasiP38532. baseline and differential.
GenevisibleiP38532. MM.


Subunit structurei

Monomer; cytoplasmic latent and transcriptionally inactive monomeric form in unstressed cells. 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. Interacts (via monomeric form) with FKBP4; this interaction occurs in unstressed cells. 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. Homotrimeric transactivation activity is modulated by protein-protein interactions and post-translational modifications. Interacts with HSP90AA1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities. 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. 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. Interacts (via homotrimeric and hyperphosphorylated form) with FKBP4; this interaction occurs upon heat shock in a HSP90-dependent multichaperone complex. Interacts (via homotrimeric form preferentially) with EEF1A proteins. 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. 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. Interacts (via D domain and preferentially with hyperphosphorylated form) with JNK1; this interaction occurs under both normal growth conditions and immediately upon heat shock. Interacts (via D domain and preferentially with hyperphosphorylated form) with MAPK3; this interaction occurs upon heat shock. Interacts with IER5 (via central region); this interaction promotes PPP2CA-induced dephosphorylation on Ser-121, Ser-307, Ser-314 and Thr-323 and HSF1 transactivation activity. 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. 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. Interacts (via Ser-303 and Ser-307 phosphorylated form) with YWHAE; this interaction promotes HSF1 sequestration in the cytoplasm in an ERK-dependent manner. Found in a complex with IER5 and PPP2CA. Interacts with TPR; this interaction increases upon heat shock and stimulates export of HSP70 mRNA. Interacts with SYMPK (via N-terminus) and CSTF2; these interactions occur upon heat shock. Interacts (via transactivation domain) with HSPA8. Interacts with EEF1D; this interaction occurs at heat shock promoter element (HSE) sequences. Interacts with MAPKAPK2. Interacts with PRKACA/PKA. Interacts (via transactivation domain) with GTF2A2. Interacts (via transactivation domain) with GTF2B. Interacts (via transactivation domain) with TBP. Interacts with CDK9, CCNT1 and EP300. 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). 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. 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. Interacts with MAD2L1; this interaction occurs in mitosis. 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. Interacts with HSP90AA1 and HSP90AB1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200443. 14 interactors.
IntActiP38532. 13 interactors.

Chemistry databases



3D structure databases


Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 120DNA-binding domainBy similarityAdd BLAST106
Regioni130 – 203Hydrophobic repeat HR-A/BBy similarityAdd BLAST74
Regioni203 – 224D domainBy similarityAdd BLAST22
Regioni221 – 310Regulatory domainBy similarityAdd BLAST90
Regioni367 – 525Transactivation domainBy similarityAdd BLAST159
Regioni380 – 405Hydrophobic repeat HR-CBy similarityAdd BLAST26


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi408 – 4169aaTADBy similarity9


In unstressed cells, spontaneous homotrimerization is inhibited. Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation. Furthermore, intramolecular interactions between the regulatory domain and the nonadjacent transactivation domain prevents transcriptional activation, a process that is relieved upon heat shock. 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. 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. The D domain is necessary for translocation to the nucleus, interaction with JNK1 and MAPK3 and efficient JNK1- and MAPK3-dependent phosphorylation. The regulatory domain confers heat shock inducibility on the transcriptional transactivation domain. The regulatory domain is necessary for transcriptional activation through its phosphorylation on Ser-230 upon heat shock. 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors.By similarity

Sequence similaritiesi

Belongs to the HSF family.Curated

Phylogenomic databases

eggNOGiKOG0627. Eukaryota.
COG5169. LUCA.

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.
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 2 (identifier: P38532-1) [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.

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510 520
Mass (Da):57,223
Last modified:August 30, 2002 - v2
Isoform 1 (identifier: P38532-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     413-434: Missing.

Show »
Mass (Da):54,931

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002416413 – 434Missing in isoform 1. 2 PublicationsAdd BLAST22

Sequence databases

Select the link destinations:
Links Updated
X61753 mRNA. Translation: CAA43892.1.
BC013716 mRNA. Translation: AAH13716.1.
AF059275 Genomic DNA. Translation: AAC80425.1.
CCDSiCCDS27572.1. [P38532-2]
RefSeqiNP_001318083.1. NM_001331154.1. [P38532-1]
NP_032322.1. NM_008296.3. [P38532-2]

Genome annotation databases

EnsembliENSMUST00000072838; ENSMUSP00000072617; ENSMUSG00000022556. [P38532-2]
UCSCiuc056yzg.1. mouse. [P38532-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiHSF1_MOUSE
AccessioniPrimary (citable) accession number: P38532
Secondary accession number(s): O70462
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: August 30, 2002
Last modified: July 5, 2017
This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome


  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families