Hsf1
entrez
15499
canonical
uniprot
P38532
canonical
ensembl
ENSMUSG00000022556
resolver
ensp
ENSMUSP00000072617
resolver
ensp
ENSMUSP00000154328
resolver
ensp
ENSMUSP00000154602
resolver
ensp
ENSMUSP00000154638
resolver
ensp
ENSMUSP00000269596
resolver
enst
ENSMUST00000226872
resolver
enst
ENSMUST00000228371
resolver
genesymbol
Hsf1
resolver
uniprot
A0A075F5C6
resolver
uniprot
A0A075F6C2
resolver
uniprot
A0A075F882
resolver
uniprot
A0A075F891
resolver
uniprot
A0A2I3BR49
resolver
uniprot
A0A2I3BRK8
resolver
uniprot
O70462
resolver
uniprot
Q52L52
resolver
uniprot_entry
A0A075F5C6_MOUSE
resolver
uniprot_entry
A0A075F6C2_MOUSE
resolver
uniprot_entry
A0A075F882_MOUSE
resolver
uniprot_entry
A0A075F891_MOUSE
resolver
uniprot_entry
A0A2I3BR49_MOUSE
resolver
uniprot_entry
A0A2I3BRK8_MOUSE
resolver
uniprot_entry
HSF1_MOUSE
resolver
uniprot_entry
Q52L52_MOUSE
resolver
uniprot_sec
O70462
resolver
amino_acid_sequence
MDLAVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKYFKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVTSVSTLKSEDIKIRQDSVTRLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHAQQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLSDSNSAHSVPKYGRQYSLEHVHGPGPYSAPSPAYSSSSLYSSDAVTSSGPIISDITELAPTSPLASPGRSIDERPLSSSTLVRVKQEPPSPPHSPRVLEASPGRPSSMDTPLSPTAFIDSILRESEPTPAASNTAPMDTTGAQAPALPTPSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLTSHGFSVDTSALLDLFSPSVTMPDMSLPDLDSSLASIQELLSPQEPPRPIEAENSNPDSGKQLVHYTAQPLFLLDPDAVDTGSSELPVLFELGESSYFSEGDDYTDDPTISLLTGTEPHKAKDPTVS
uniprot
proteins
function
FUNCTION: Functions 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 insult 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. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival. 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. Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 (By similarity). Binds the promoter region upstream of exon 1 of Mpv17l to activate expression of the M-LPS isoform which is involved in metabolism of reactive oxygen species (PubMed:20231359). Also serves 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. Also plays 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. {ECO:0000250|UniProtKB:Q00613, ECO:0000269|PubMed:20231359}.
uniprot
proteins
mass_dalton
57223
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250|UniProtKB:Q00613}.; PTM: 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. {ECO:0000250|UniProtKB:Q00613}.; PTM: 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. {ECO:0000250|UniProtKB:Q00613}.; PTM: 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. {ECO:0000250|UniProtKB:Q00613}.
uniprot
proteins
protein_family
HSF family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1717345
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
20231359
uniprot
proteins
pubmed
26159920
uniprot
proteins
pubmed
9829985
uniprot
proteins
sequence_length
525
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26159920}. Cytoplasm {ECO:0000269|PubMed:26159920}. Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q00613}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q00613}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q00613}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q00613}. Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:Q00613}. 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. {ECO:0000250|UniProtKB:Q00613, ECO:0000269|PubMed:26159920}.
uniprot
proteins