HSF1
entrez
3297
canonical
uniprot
Q00613
canonical
ensembl
ENSG00000185122
resolver
ensembl
ENSG00000284774
resolver
ensp
ENSP00000431512
resolver
ensp
ENSP00000532656
resolver
ensp
ENSP00000669577
resolver
ensp
ENSP00000669580
resolver
ensp
ENSP00000689981
resolver
ensp
ENSP00000760050
resolver
ensp
ENSP00000760051
resolver
genesymbol
HSF1
resolver
genesymbol_syn
HSTF1
resolver
hgnc
HGNC:5224
resolver
uniprot
A8K4L0
resolver
uniprot
A8MW26
resolver
uniprot
Q53XT4
resolver
uniprot_entry
HSF1_HUMAN
resolver
uniprot_sec
A8K4L0
resolver
uniprot_sec
A8MW26
resolver
uniprot_sec
Q53XT4
resolver
amino_acid_sequence
MDLPVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKYFKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVTSVSTLKSEDIKIRQDSVTKLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHAQQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLNDSGSAHSMPKYSRQFSLEHVHGSGPYSAPSPAYSSSSLYAPDAVASSGPIISDITELAPASPMASPGGSIDERPLSSSPLVRVKEEPPSPPQSPRVEEASPGRPSSVDTLLSPTALIDSILRESEPAPASVTALTDARGHTDTEGRPPSPPPTSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLSSHGFSVDTSALLDLFSPSVTVPDMSLPDLDSSLASIQELLSPQEPPRPPEAENSSPDSGKQLVHYTAQPLFLLDPGSVDTGSNDLPVLFELGEGSYFSEGDGFAEDPTISLLTGSEPPKAKDPTVS
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 (PubMed:11447121, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:18451878, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7760831, PubMed:8940068, PubMed:8946918, PubMed:9121459, PubMed:9341107, PubMed:9499401, PubMed:9535852, PubMed:9727490). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:11583998, PubMed:16278218, PubMed:9727490). 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:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7935471, PubMed:8455624, PubMed:8940068, PubMed:9499401, PubMed:9727490). Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival (PubMed:18451878). 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). 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 (PubMed:34723967). 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 (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). Also plays 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). {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12659875, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:1871105, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:1986252, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26727489, ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:34723967, ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831, ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624, ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9341107, ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9535852, ECO:0000269|PubMed:9727490}.; FUNCTION: (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. {ECO:0000269|PubMed:27189267}.
uniprot
proteins
mass_dalton
57260
uniprot
proteins
mutagenesis
MUTAGEN 22; /note="L->A: Inhibits HSEDNA-binding activity and transcriptional activation."; /evidence="ECO:0000269|PubMed:9341107"; MUTAGEN 80; /note="K->Q: Loss of nuclear stress bodies localization. Loss of DNA-binding and transcriptional activities upon heat shock. No change in homotrimerization upon heat shock."; /evidence="ECO:0000269|PubMed:19229036, ECO:0000269|PubMed:24581496"; MUTAGEN 80; /note="K->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."; /evidence="ECO:0000269|PubMed:19229036, ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:26359349"; MUTAGEN 91; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:12665592"; MUTAGEN 118; /note="K->Q: Loss of nuclear stress bodies localization. No change in protein abundance."; /evidence="ECO:0000269|PubMed:24581496"; MUTAGEN 118; /note="K->R: No change in nuclear stress bodies localization."; /evidence="ECO:0000269|PubMed:24581496"; MUTAGEN 120; /note="T->A: No effect on binding HSE nor on transcriptional activity."; /evidence="ECO:0000269|PubMed:16278218"; MUTAGEN 121; /note="S->A: Increased binding HSE and transcriptional activity. Greatly reduced binding to HSP90AA1. No effect on MAPKAPK2 binding."; /evidence="ECO:0000269|PubMed:16278218"; MUTAGEN 121; /note="S->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."; /evidence="ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:26754925"; MUTAGEN 123; /note="S->A: No effect on binding HSE nor on transcriptional activity."; /evidence="ECO:0000269|PubMed:16278218"; MUTAGEN 124; /note="T->A: No effect on binding HSE nor on transcriptional activity."; /evidence="ECO:0000269|PubMed:16278218"; MUTAGEN 126; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:12665592"; MUTAGEN 140; /note="L->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."; /evidence="ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7935471"; MUTAGEN 142; /note="T->A: Reduced promoter activity by about 90%. Almost no transcriptional activity when coexpressed with CK2."; /evidence="ECO:0000269|PubMed:12659875"; MUTAGEN 147; /note="M->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."; /evidence="ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7935471"; MUTAGEN 147; /note="M->E: Does not lead to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Loss of DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 147; /note="M->K: Does not lead to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Loss of DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 150; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:12665592"; MUTAGEN 162; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:12665592"; MUTAGEN 189; /note="L->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."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 189; /note="L->E: Leads to constitutive homotrimerization, DNA-binding and transactivation activities at 20 degrees Celsius. Decreased DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7935471"; MUTAGEN 189; /note="L->K: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 193; /note="L->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."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 193; /note="L->E: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Decreased DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 193; /note="L->K: Leads to constitutive homotrimerization and DNA-binding activities at 20 degrees Celsius. Loss of DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 208; /note="K->Q: No change in nuclear stress bodies localization. Increased protein abundance."; /evidence="ECO:0000269|PubMed:24581496"; MUTAGEN 208; /note="K->R: No change in nuclear stress bodies localization. No change in protein abundance."; /evidence="ECO:0000269|PubMed:24581496"; MUTAGEN 216; /note="S->A: Does not change interaction with XRCC5 and XRCC6. No PLK1-induced phosphorylation in mitosis. Inhibits PLK1-stimulated ubiquitinylation. Increased protein stability."; /evidence="ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:26359349"; MUTAGEN 216; /note="S->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."; /evidence="ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:26359349"; MUTAGEN 216; /note="S->N: Decreased spindle pole localization. Decreased interaction with BTRC. Increased protein stability."; /evidence="ECO:0000269|PubMed:18794143"; MUTAGEN 230; /note="S->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."; /evidence="ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143"; MUTAGEN 230; /note="S->D: Mimics phosphorylation. No effect on transcriptional activity upon heat shock."; /evidence="ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:12665592"; MUTAGEN 275; /note="S->A: Reduced increase in heat-induced transcriptional activity."; /evidence="ECO:0000269|PubMed:9535852"; MUTAGEN 275; /note="S->G: Leads to weak constitutive transactivation activity at room temperature."; /evidence="ECO:0000269|PubMed:8940068"; MUTAGEN 292; /note="S->A: Weak decreased PLK1-induced phosphorylation. Increased nuclear localization upon heat shock."; /evidence="ECO:0000269|PubMed:15661742"; MUTAGEN 296; /note="R->A: No effect neither on repression of transcriptional activity at control temperature nor on transcriptional activation upon heat shock."; /evidence="ECO:0000269|PubMed:8946918"; MUTAGEN 297; /note="V->A: Slight effect on derepression of transcriptional activity at control temperature and on transcriptional activation upon heat shock."; /evidence="ECO:0000269|PubMed:8946918"; MUTAGEN 298; /note="K->A: Induces derepression of transcriptional activity at control temperature."; /evidence="ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:8946918"; MUTAGEN 298; /note="K->Q: No change in nuclear stress bodies localization. Increased protein abundance."; /evidence="ECO:0000269|PubMed:24581496"; MUTAGEN 298; /note="K->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."; /evidence="ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:8946918"; MUTAGEN 299; /note="E->A: No effect on repression of transcriptional activity at control temperature."; /evidence="ECO:0000269|PubMed:8946918"; MUTAGEN 300; /note="E->A: Induces derepression of transcriptional activity at control temperature."; /evidence="ECO:0000269|PubMed:8946918"; MUTAGEN 303; /note="S->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."; /evidence="ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9535852"; MUTAGEN 303; /note="S->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."; /evidence="ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9535852"; MUTAGEN 303; /note="S->G: Leads to constitutive transactivation activity at room temperature. Inhibits interaction with YWHAE and increases cytoplasmic localization; when associated with G-307."; /evidence="ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:8940068"; MUTAGEN 307; /note="S->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."; /evidence="ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9535852"; MUTAGEN 307; /note="S->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."; /evidence="ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459"; MUTAGEN 307; /note="S->G: Leads to constitutive transactivation activity at room temperature. Inhibits interaction with YWHAE and increases cytoplasmic localization; when associated with G-303."; /evidence="ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:8940068"; MUTAGEN 309; /note="R->A: No effect on repression of transcriptional activity at control temperature."; /evidence="ECO:0000269|PubMed:8946918"; MUTAGEN 311; /note="E->A: No effect neither on repression of transcriptional activity at control temperature nor on transcriptional activation upon heat shock."; /evidence="ECO:0000269|PubMed:8946918"; MUTAGEN 314; /note="S->A: Weak decreased PLK1-induced phosphorylation."; /evidence="ECO:0000269|PubMed:15661742"; MUTAGEN 314; /note="S->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."; /evidence="ECO:0000269|PubMed:26754925"; MUTAGEN 319; /note="S->A: Weak decreased PLK1-induced phosphorylation."; /evidence="ECO:0000269|PubMed:15661742"; MUTAGEN 320; /note="S->A: Decreased nuclear localization and transcriptional activity upon heat shock."; /evidence="ECO:0000269|PubMed:21085490"; MUTAGEN 320; /note="S->D: Increased nuclear localization and transcriptional activity upon heat shock."; /evidence="ECO:0000269|PubMed:21085490"; MUTAGEN 323; /note="T->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."; /evidence="ECO:0000269|PubMed:26754925"; MUTAGEN 326; /note="S->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."; /evidence="ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:15760475, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066"; MUTAGEN 326; /note="S->E: Does not change interaction with XRCC5 and XRCC6."; /evidence="ECO:0000269|PubMed:26359349"; MUTAGEN 363; /note="S->A: Decreases MAPK8-induced phosphorylation and does not negatively regulates transactivating activity upon heat shock. No effect on sumoylation."; /evidence="ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:12665592"; MUTAGEN 367; /note="T->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."; /evidence="ECO:0000269|PubMed:26754925"; MUTAGEN 381; /note="K->R: No effect on sumoylation."; /evidence="ECO:0000269|PubMed:12665592"; MUTAGEN 391; /note="M->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."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 391; /note="M->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."; /evidence="ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7935471"; MUTAGEN 391; /note="M->K: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 395; /note="L->E: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 395; /note="L->K: Leads to constitutive DNA-binding and homotrimerization activities at 20 degrees Celsius. No effect on DNA-binding activity at 37 degrees Celsius."; /evidence="ECO:0000269|PubMed:7935471"; MUTAGEN 419; /note="S->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."; /evidence="ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:26359349"; MUTAGEN 419; /note="S->E: Does not change interaction with XRCC5 and XRCC6."; /evidence="ECO:0000269|PubMed:26359349"; MUTAGEN 527; /note="T->A: No change in binding HSE nor on transcriptional activity. Decreased binding HSE; when associated with A-529."; /evidence="ECO:0000269|PubMed:16278218"; MUTAGEN 529; /note="S->A: No change in binding HSE nor on transcriptional activity. Decreased binding HSE; when associated with A-527."; /evidence="ECO:0000269|PubMed:16278218
uniprot
proteins
post_translational_modification
PTM: Phosphorylated (PubMed:10359787, PubMed:11583998, PubMed:26159920, PubMed:9499401). Phosphorylated in unstressed cells; this phosphorylation is constitutive and implicated in the repression of HSF1 transcriptional activity (PubMed:16278218, PubMed:8940068, PubMed:8946918, PubMed:9121459). 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:10747973, PubMed:12646186, PubMed:8940068, PubMed:8946918, PubMed:9121459, PubMed:9535852). 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). {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12659875, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:15760475, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9535852}.; PTM: 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). {ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592}.; PTM: 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). {ECO:0000269|PubMed:19229036, ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27189267}.; PTM: 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). {ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:24581496}.
uniprot
proteins
protein_family
HSF family
uniprot
proteins
pubmed
10359787
uniprot
proteins
pubmed
10413683
uniprot
proteins
pubmed
10747973
uniprot
proteins
pubmed
11005381
uniprot
proteins
pubmed
11447121
uniprot
proteins
pubmed
11514557
uniprot
proteins
pubmed
11583998
uniprot
proteins
pubmed
12646186
uniprot
proteins
pubmed
12659875
uniprot
proteins
pubmed
12665592
uniprot
proteins
pubmed
12917326
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14707147
uniprot
proteins
pubmed
15016915
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15661742
uniprot
proteins
pubmed
15760475
uniprot
proteins
pubmed
16278218
uniprot
proteins
pubmed
16371476
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16554823
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17467953
uniprot
proteins
pubmed
17897941
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18451878
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
1871105
uniprot
proteins
pubmed
1871106
uniprot
proteins
pubmed
18794143
uniprot
proteins
pubmed
19229036
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
1986252
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21085490
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21597468
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24581496
uniprot
proteins
pubmed
25816751
uniprot
proteins
pubmed
25963659
uniprot
proteins
pubmed
26159920
uniprot
proteins
pubmed
26359349
uniprot
proteins
pubmed
26496226
uniprot
proteins
pubmed
26517842
uniprot
proteins
pubmed
26727489
uniprot
proteins
pubmed
26754925
uniprot
proteins
pubmed
27189267
uniprot
proteins
pubmed
27354066
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
34723967
uniprot
proteins
pubmed
7623826
uniprot
proteins
pubmed
7760831
uniprot
proteins
pubmed
7935376
uniprot
proteins
pubmed
7935471
uniprot
proteins
pubmed
8455624
uniprot
proteins
pubmed
8940068
uniprot
proteins
pubmed
8946918
uniprot
proteins
pubmed
9121459
uniprot
proteins
pubmed
9222587
uniprot
proteins
pubmed
9341107
uniprot
proteins
pubmed
9499401
uniprot
proteins
pubmed
9535852
uniprot
proteins
pubmed
9727490
uniprot
proteins
sequence_length
529
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10413683, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:19229036, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27189267, ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:8455624}. Cytoplasm {ECO:0000269|PubMed:10413683, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:8455624}. Nucleus, nucleoplasm {ECO:0000269|PubMed:10359787}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:21085490}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:18794143}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:18794143}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:18794143}. Note=The monomeric form is cytoplasmic in unstressed cells (PubMed:26159920, PubMed:8455624). Predominantly nuclear protein in both unstressed and heat shocked cells (PubMed:10359787, PubMed:10413683). Translocates in the nucleus upon heat shock (PubMed:8455624). Nucleocytoplasmic shuttling protein (PubMed:26159920). Colocalizes with IER5 in the nucleus (PubMed:27354066). Colocalizes with BAG3 to the nucleus upon heat stress (PubMed:26159920, PubMed:8455624). Localizes in subnuclear granules called nuclear stress bodies (nSBs) upon heat shock (PubMed:10359787, PubMed:10747973, PubMed:11447121, PubMed:11514557, PubMed:19229036, PubMed:24581496, PubMed:25963659). Colocalizes with SYMPK and SUMO1 in nSBs upon heat shock (PubMed:10359787, PubMed:11447121, PubMed:11514557, PubMed:12665592, PubMed:14707147). Colocalizes with PRKACA/PKA in the nucleus and nSBs upon heat shock (PubMed:21085490). Relocalizes from the nucleus to the cytoplasm during the attenuation and recovery phase period of the heat shock response (PubMed:26159920). Translocates in the cytoplasm in a YWHAE- and XPO1/CRM1-dependent manner (PubMed:12917326). Together with histone H2AX, redistributed in discrete nuclear DNA damage-induced foci after ionizing radiation (IR) (PubMed:26359349). Colocalizes with calcium-responsive transactivator SS18L1 at kinetochore region on the mitotic chromosomes (PubMed:18794143). Colocalizes with gamma tubulin at centrosome (PubMed:18794143). Localizes at spindle pole in metaphase (PubMed:18794143). Colocalizes with PLK1 at spindle poles during prometaphase (PubMed:18794143). {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:10413683, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:8455624}.
uniprot
proteins