HSF1

Summary

HSF1 (heat shock transcription factor 1, HGNC:5224) is a protein-coding gene on chromosome 8q24.3, encoding Heat shock factor protein 1 (Q00613). 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 f…. It is a selective cancer dependency (DepMap: 45.0% of cell lines).

The product of this gene is a transcription factor that is rapidly induced after temperature stress and binds heat shock promoter elements (HSE). This protein plays a role in the regulation of lifespan. Expression of this gene is repressed by phosphorylation, which promotes binding by heat shock protein 90.

Source: NCBI Gene 3297 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 95 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 45.0% of screened cell lines
• Transcription factor: yes — 108 downstream targets (CollecTRI)
• MANE Select transcript: NM_005526

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5224
Approved symbol	HSF1
Name	heat shock transcription factor 1
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	HSTF1
Ensembl gene	ENSG00000185122
Ensembl biotype	protein_coding
OMIM	140580
Entrez	3297

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 19 protein_coding, 8 retained_intron, 3 nonsense_mediated_decay

ENST00000400780, ENST00000527328, ENST00000528199, ENST00000528838, ENST00000528842, ENST00000528988, ENST00000529630, ENST00000530661, ENST00000531447, ENST00000532338, ENST00000533130, ENST00000533240, ENST00000534314, ENST00000614796, ENST00000862597, ENST00000862598, ENST00000862599, ENST00000862600, ENST00000862601, ENST00000862602, ENST00000862603, ENST00000862604, ENST00000862605, ENST00000912476, ENST00000960346, ENST00000960347, ENST00000960348, ENST00000960349, ENST00000960350, ENST00000960351

RefSeq mRNA: 1 — MANE Select: NM_005526 NM_005526

CCDS: CCDS6419

Canonical transcript exons

ENST00000528838 — 13 exons

Exon	Start	End
ENSE00001646174	144309455	144309591
ENSE00002175525	144291604	144291874
ENSE00002191910	144314125	144314720
ENSE00003497343	144308906	144309014
ENSE00003507105	144313511	144313616
ENSE00003548194	144311700	144311836
ENSE00003562204	144309772	144309896
ENSE00003584099	144313985	144314054
ENSE00003584809	144311963	144312244
ENSE00003592683	144311505	144311601
ENSE00003610382	144311174	144311249
ENSE00003624520	144313846	144313911
ENSE00003646326	144311321	144311382

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.4568 / max 565.2428, expressed in 1823 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91486	75.1585	1822
91488	0.7130	446
91493	0.6309	396
91491	0.5301	257
91492	0.1637	54
205400	0.1188	38
91489	0.0716	9
91490	0.0703	15

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.55	gold quality
left testis	UBERON:0004533	98.26	gold quality
right testis	UBERON:0004534	98.20	gold quality
heart left ventricle	UBERON:0002084	97.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.49	gold quality
right atrium auricular region	UBERON:0006631	97.39	gold quality
stromal cell of endometrium	CL:0002255	97.08	gold quality
heart	UBERON:0000948	97.04	gold quality
gastrocnemius	UBERON:0001388	96.95	gold quality
testis	UBERON:0000473	96.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.85	gold quality
lower esophagus	UBERON:0013473	96.84	gold quality
popliteal artery	UBERON:0002250	96.80	gold quality
tibial artery	UBERON:0007610	96.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.73	gold quality
fundus of stomach	UBERON:0001160	96.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.60	gold quality
body of stomach	UBERON:0001161	96.54	gold quality
muscle of leg	UBERON:0001383	96.44	gold quality
skeletal muscle tissue	UBERON:0001134	96.38	gold quality
right coronary artery	UBERON:0001625	96.27	gold quality
prostate gland	UBERON:0002367	96.23	gold quality
body of pancreas	UBERON:0001150	96.16	gold quality
skin of leg	UBERON:0001511	96.16	gold quality
left coronary artery	UBERON:0001626	96.15	gold quality
left uterine tube	UBERON:0001303	96.11	gold quality
mucosa of stomach	UBERON:0001199	96.10	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.10	gold quality
right lung	UBERON:0002167	96.09	gold quality
pituitary gland	UBERON:0000007	96.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.58
E-MTAB-9388	yes	7.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

108 targets.

Target	Regulation
ABCB1	Unknown
ABCB6
ADAM2
ATF3	Unknown
ATG7	Activation
BACE1
BAG3	Repression
CDKN1A	Repression
CDKN1B
CLU	Activation
CRYAB	Activation
CRYGA	Unknown
CRYGB	Unknown
CRYGC
CSF1R	Repression
CSF2
CSF3	Activation
CXCL1	Activation
CXCL2	Activation
CXCL3
CXCL5	Activation
CXCL8	Activation
CYLC1
DLG1	Activation
DNAJB1	Activation
ERBB2
EYA1
FAS	Unknown
FASLG
FKBP4	Unknown

JASPAR motifs

Motif	Name	Family
MA0486.1	HSF1	HSF factors
MA0486.2	HSF1	HSF factors

JASPAR matrix evidence (PMIDs): PMID:17500587

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, HIF1A, HSF1, NCOA6, NFATC2, NFIX, NFKB, SIRT1, SP1, TP53, TP73, YY1

miRNA regulators (miRDB)

19 targeting HSF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-10525-3P	96.32	68.04	699

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6 (PMID:11801594)
• Retrovirus-mediated transfer of dominant-negative mutant HSF1 leads to massive cell death of breast cancer cells after hyperthermia treatment. (PMID:11820785)
• redox-dependent thiol-disulfide exchange in regulating conformation and activity (PMID:11851405)
• HSF1 granules localize to the 9q11-q12 heterochromatic region. Within this locus, HSF1 binds through direct DNA-protein interaction with a nucleosome-containing subclass of satellite III repeats. (PMID:11877455)
• Binding of the heat shock element of HSP47 by HSF1 is enhanced by TGF-beta or IL-1 beta and is augmented by a combination of both cytokines. (PMID:11994473)
• HSF1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes (PMID:12468538)
• examination of the role of the phosphorylation event in regulating SUMO-1 modification of HSF1 (PMID:12646186)
• HSF1 activation by heat is correlated with the thermal activation of nuclear CK2 and overexpression of CK2 activates HSF1 (PMID:12659875)
• HSF1 is modified by SUMO-1 and SUMO-2 in a stress-inducible manner. (PMID:12665592)
• elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced transcription during oxidative stress in cancer cells (PMID:12813038)
• modified heat shock factor can suppress HIV1 promoter activity by a mechanism involving interaction with Sp1 elements in the HIV1 promoter (PMID:12878154)
• HSF1 binding to 14-3-3 epsilon requires HSF1 phosphorylation on serines 303 and 307, the serine phosphorylation-dependent binding of HSF1 to 14-3-3 epsilon results in the transcriptional repression of HSF1 and its sequestration in the cytoplasm. (PMID:12917326)
• HSF1 does not have a role in transcriptional regulation of the human RANK ligand gene (PMID:14699143)
• HSF1 regulates HSP gene expression at not one but two different steps of the expression pathway, functioning both as a transcription factor and a polyadenylation stimulatory factor (PMID:14707147)
• HSF is an important transcription factor involved in up-regulation of VDUP1 expression by stresses such as high density and serum deprivation cultures (PMID:14766217)
• results suggest that ASC-2 is a novel coactivator for HSF1 and heat shock stress may contribute to the strong active transcription complex through sequential recruitment of HSF1 and ASC-2. (PMID:14960326)
• regulation by N-terminal truncated form of p73alpha (PMID:15081420)
• HSF1 plays a functional role in cancer cells under nonstress conditions and influences cell cycle behavior and progression through mitosis and promotes the development of the aneuploid state (PMID:15152009)
• Results suggest that mutant HSF1 abolishes thermotolerance in Bcap37 cells by enhancing Jun kinase and caspase-3 pathways after hyperthermia. (PMID:15358168)
• HSF1 associates with ERK1 and 14-3-3epsilon during heat shock to modulate the amplitude of the response and lead to efficient termination of HSP expression on resumption of growth conditions (PMID:15364926)
• The induction of HSF1 gene expression is associated with sporadic colon cancer. (PMID:15457556)
• phosphorylation of HSF1 by PLK1 is an essential step for HSF1 nuclear translocation by heat stress (PMID:15661742)
• Inactive, stress-responsive form of HSF1 accumulates in the nucleus due to a relatively potent import signal, which can be recognized by importin-alpha/beta, and simultaneously undergoes continuous nucleocytoplasmic shuttling. (PMID:15702990)
• Phosphorylation of HSF1 residue serine326 plays a critical role in the induction of the factor’s transcriptional competence by heat stress; phosphoSer326 also contributes to activation of HSF1 by chemical stress (PMID:15760475)
• Hsp90 is involved in hsp70 mRNA stabilisation and the HSF1 activation can be suppressed by high hydrostatic pressure (PMID:15777846)
• HSF1 has a strong inhibitory effect on polyglutamine aggregate formation in vivo and in vitro (PMID:16051598)
• HSF1 phosphorylation by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding (PMID:16278218)
• CHIP directly interacts with C-terminal deleted HSF1 but not with full-length HSF1 under non-stressed conditions, and with full-length HSF1 under heat shock treatment; interaction requires conformational change of HSF1 by heat stress. (PMID:16293251)
• endogenous stress pressure in cancer cells sustained the high level expression of HSF1 and subsequently suppressed XAF1 expression, implicating the synergized effect of two anti-apoptotic protein families in cytoprotection under stress circumstances (PMID:16303760)
• HSF1 can activate MDR-1 expression in a stress-independent manner that differs from the canonical heat shock-activated mechanism involved in HSP induction. (PMID:16382149)
• Both NF-kappaB and HSF-1 are systemically activated in human acute pancreatitis. HSF-1 activation may protect against severity of pancreatitis. (PMID:16525201)
• HSP25 and HSP70i activate HSF1 and have roles in inhibition of ERK1/2 phosphorylation (PMID:16624816)
• Wild-type and constitutively active forms of HSF1 induce anticoagulation and relaxation factors in vascular endothelial cells and could therefore be used to treat cardiovascular disease. (PMID:16678833)
• Both HSF1 and HSF2 were able to bind the hsp70 promoter not only in response to heat shock but also during hemin-induced differentiation of K562 erythroleukemia cells. (PMID:17213196)
• identification of genes regulated directly and indirectly by HSF1 (PMID:17216044)
• HSF1 is directly involved in the regulation of HO-1 with an anti-oxidative role (PMID:17244614)
• IL-6, via the PI3-kinase/Akt pathway leads to inhibition of the repressive kinases MAPK/pERK and GSK3beta, and this converts inactive HSF-1 to an intermediate DNA-binding form augmenting transcriptional activation in the presence of a second stressor. (PMID:17273789)
• activation of HSF1 and stabilization of Bcl-X(L) mediate a protective response that may contribute significantly to the cellular biology of lipid peroxidation (PMID:17873279)
• The high expression of HSF1 in gastro-intestinal cancer is associated with suppressed expression of XAF1. (PMID:17884799)
• Human cancer lines of diverse origins show much greater dependence on HSF1 function to maintain proliferation and survival than their nontransformed counterparts. (PMID:17889646)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hsf1	ENSMUSG00000022556
rattus_norvegicus	Hsf1	ENSRNOG00000021732
drosophila_melanogaster	Hsf	FBGN0001222
caenorhabditis_elegans	hsf-1	WBGENE00002004

Paralogs (9): HSF2 (ENSG00000025156), HSF4 (ENSG00000102878), HSFY2 (ENSG00000169953), HSFX1 (ENSG00000171116), HSFY1 (ENSG00000172468), HSF5 (ENSG00000176160), HSFX2 (ENSG00000268738), HSFX4 (ENSG00000283463), HSFX3 (ENSG00000283697)

Protein

Protein identifiers

Heat shock factor protein 1 — Q00613 (reviewed: Q00613)

Alternative names: Heat shock transcription factor 1

All UniProt accessions (6): A0A087WWQ3, A0A087WXG6, A0A087X1F9, E9PI02, E9PMQ6, Q00613

UniProt curated annotations — full annotation on UniProt →

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. 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. (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.

Subunit / interactions. 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, Thr-323 and Thr-367 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. Forms a complex with TTC5/STRAP and p300/EP300; these interactions augment chromatin-bound HSF1 and p300/EP300 histone acetyltransferase activity.

Subcellular location. Nucleus. Cytoplasm. Nucleoplasm. Perinuclear region. Cytoskeleton. Spindle pole. Microtubule organizing center. Centrosome. Chromosome. Centromere. Kinetochore.

Post-translational modifications. 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-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. 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 PubMed:9535852, Ser-303 is not phosphorylated in unstressed cells. Phosphorylated on Ser-419 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 on Ser-363 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-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. 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, Thr-323 and Thr-367 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity. 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. 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. 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.

Domain organisation. 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.

Similarity. Belongs to the HSF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q00613-1	Long	yes
Q00613-2	Short

RefSeq proteins (1): NP_005517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000232	HSF_DNA-bd	Domain
IPR010542	Vert_HSTF_C	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00447, PF06546

UniProt features (130 total): mutagenesis site 70, modified residue 26, region of interest 10, cross-link 7, helix 6, strand 6, splice variant 2, chain 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5HDN	X-RAY DIFFRACTION	1.68
5HDG	X-RAY DIFFRACTION	1.7
7DCJ	X-RAY DIFFRACTION	2
7DCT	X-RAY DIFFRACTION	2.36
7DCS	X-RAY DIFFRACTION	2.4
5D5V	X-RAY DIFFRACTION	2.55
5D5U	X-RAY DIFFRACTION	2.91
2LDU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00613-F1	62.61	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (33): 1, 80, 91, 118, 121, 142, 150, 188, 208, 216, 230, 275, 292, 298, 303, 307, 314, 319, 320, 323 …

Mutagenesis-validated functional residues (70):

Position	Phenotype
320	decreased nuclear localization and transcriptional activity upon heat shock.
320	increased nuclear localization and transcriptional activity upon heat shock.
323	decreased hsf1-induced expression of hspa1a mrna in a ier5-dependent manner; when associated with d-121; d-307; d-314 an
326	no phosphorylation. increased nuclear localization upon heat shock. no effect on oligomerization, dna-binding activities
326	does not change interaction with xrcc5 and xrcc6.
363	decreases mapk8-induced phosphorylation and does not negatively regulates transactivating activity upon heat shock. no e
367	decreased hsf1-induced expression of hspa1a mrna in a ier5-dependent manner; when associated with d-121; d-307; d-314 an
381	no effect on sumoylation.
391	does not lead to constitutive dna-binding activity at 20 degrees celsius. leads to weak constitutive dna-binding and hom
391	leads to constitutive dna-binding and homotrimerization activities at 20 degrees celsius. does not lead to constitutive
391	leads to constitutive dna-binding and homotrimerization activities at 20 degrees celsius. no effect on dna-binding activ
395	leads to constitutive dna-binding and homotrimerization activities at 20 degrees celsius. no effect on dna-binding activ
419	does not change interaction with xrcc5 and xrcc6. decreased nuclear localization upon heat shock. strongly decreases plk
419	does not change interaction with xrcc5 and xrcc6.
527	no change in binding hse nor on transcriptional activity. decreased binding hse; when associated with a-529.
529	no change in binding hse nor on transcriptional activity. decreased binding hse; when associated with a-527.
22	inhibits hse dna-binding activity and transcriptional activation.
80	loss of nuclear stress bodies localization. loss of dna-binding and transcriptional activities upon heat shock. no chang
80	does not change interaction with xrcc5 and xrcc6. loss of nuclear stress bodies localization. decreased nuclear stress b
91	no effect on sumoylation.
118	loss of nuclear stress bodies localization. no change in protein abundance.
118	no change in nuclear stress bodies localization.
120	no effect on binding hse nor on transcriptional activity.
121	increased binding hse and transcriptional activity. greatly reduced binding to hsp90aa1. no effect on mapkapk2 binding.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-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
R-HSA-9646399	Aggrephagy
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)

MSigDB gene sets: 299 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, ELVIDGE_HYPOXIA_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_GROWTH, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_CELLULAR_RESPONSE_TO_GAMMA_RADIATION

GO Biological Process (62): negative regulation of transcription by RNA polymerase II (GO:0000122), MAPK cascade (GO:0000165), embryonic placenta development (GO:0001892), DNA repair (GO:0006281), regulation of transcription by RNA polymerase II (GO:0006357), mRNA processing (GO:0006397), defense response (GO:0006952), female meiotic nuclear division (GO:0007143), spermatogenesis (GO:0007283), response to nutrient (GO:0007584), positive regulation of gene expression (GO:0010628), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), response to activity (GO:0014823), negative regulation of protein-containing complex assembly (GO:0031333), negative regulation of tumor necrosis factor production (GO:0032720), response to testosterone (GO:0033574), cellular response to heat (GO:0034605), cellular response to unfolded protein (GO:0034620), cellular response to potassium ion (GO:0035865), positive regulation of multicellular organism growth (GO:0040018), positive regulation of macrophage differentiation (GO:0045651), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of transcription by RNA polymerase II (GO:0045944), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), mRNA transport (GO:0051028), embryonic process involved in female pregnancy (GO:0060136), positive regulation of stress granule assembly (GO:0062029), protein-containing complex assembly (GO:0065003), cellular response to hydrogen peroxide (GO:0070301), cellular response to lipopolysaccharide (GO:0071222), cellular response to cadmium ion (GO:0071276), cellular response to copper ion (GO:0071280), cellular response to estradiol stimulus (GO:0071392), cellular response to xenobiotic stimulus (GO:0071466), cellular response to gamma radiation (GO:0071480), cellular response to diamide (GO:0072738), negative regulation of inclusion body assembly (GO:0090084), positive regulation of inclusion body assembly (GO:0090261), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (23): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding (GO:0001162), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein kinase binding (GO:0019901), heat shock protein binding (GO:0031072), chromatin DNA binding (GO:0031490), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), protein heterodimerization activity (GO:0046982), Hsp90 protein binding (GO:0051879), translation elongation factor binding (GO:0061770), STAT family protein binding (GO:0097677), sequence-specific single stranded DNA binding (GO:0098847), general transcription initiation factor binding (GO:0140296), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (21): kinetochore (GO:0000776), chromatin (GO:0000785), euchromatin (GO:0000791), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), PML body (GO:0016605), pronucleus (GO:0045120), perinuclear region of cytoplasm (GO:0048471), nuclear stress granule (GO:0097165), mitotic spindle pole (GO:0097431), protein folding chaperone complex (GO:0101031), ribonucleoprotein complex (GO:1990904), chromosome, centromeric region (GO:0000775), spindle pole (GO:0000922), chromosome (GO:0005694), cytoskeleton (GO:0005856), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cellular response to heat stress	3
HSF1-dependent transactivation	1
Selective autophagy	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
RNA polymerase II transcription regulatory region sequence-specific DNA binding	5
chromatin	3
protein binding	3
intracellular membraneless organelle	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
DNA binding	2
sequence-specific DNA binding	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
intracellular signaling cassette	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
DNA metabolic process	1
DNA damage response	1
RNA processing	1
mRNA metabolic process	1
response to stress	1
female gamete generation	1
meiotic cell cycle	1
meiotic nuclear division	1
developmental process involved in reproduction	1
male gamete generation	1
response to nutrient levels	1
response to chemical	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
response to stimulus	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
tumor necrosis factor production	1

Protein interactions and networks

STRING

1401 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSF1	HSP90AA1	P07900	957
HSF1	HSP90AB1	P08238	957
HSF1	HSPA4	P34932	943
HSF1	GNL1	P36915	839
HSF1	HSPB1	P04792	725
HSF1	DNAJB1	P25685	724
HSF1	BOP1	Q14137	655
HSF1	HSPA1A	P08107	624
HSF1	ZC3HAV1	Q7Z2W4	608
HSF1	HSPB2	Q16082	604
HSF1	HSPB3	Q12988	583
HSF1	EEF1A1	P04719	566
HSF1	BAG1	Q99933	531
HSF1	MYC	P01106	512
HSF1	HSPA8	P11142	512

IntAct

136 interactions, top by confidence:

A	B	Type	Score
HSF1	HSF2	psi-mi:“MI:0915”(physical association)	0.880
HSF1	HSF2	psi-mi:“MI:0407”(direct interaction)	0.880
HSF2	HSF1	psi-mi:“MI:0915”(physical association)	0.880
PLK1	SPAG9	psi-mi:“MI:0914”(association)	0.790
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
HSF1	KPNA3	psi-mi:“MI:0914”(association)	0.640
HSF1	MAPKAPK2	psi-mi:“MI:0915”(physical association)	0.600
HSF1	MAPKAPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
MAPKAPK2	HSF1	psi-mi:“MI:0915”(physical association)	0.600
HSF1	IER5	psi-mi:“MI:0915”(physical association)	0.590
IER5	HSF1	psi-mi:“MI:0915”(physical association)	0.590
HSF1	HSF1	psi-mi:“MI:0407”(direct interaction)	0.570
HSF1	HSF1	psi-mi:“MI:2364”(proximity)	0.570
	HSF1	psi-mi:“MI:0915”(physical association)	0.560
SCGB1A1	HSF1	psi-mi:“MI:0915”(physical association)	0.560
HSF1	ZNF232	psi-mi:“MI:0915”(physical association)	0.560
HSF1	PRMT5	psi-mi:“MI:0915”(physical association)	0.560
HSF1	LPIN1	psi-mi:“MI:0915”(physical association)	0.560
HSF1	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
HSF1	KLF15	psi-mi:“MI:0915”(physical association)	0.560
HSF1	TMEM185A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (778): HSF1 (Affinity Capture-Western), NCOA6 (Reconstituted Complex), CREBBP (Reconstituted Complex), NCOA6 (Affinity Capture-Western), HSF1 (Affinity Capture-Western), HSF1 (Reconstituted Complex), HSF1 (Affinity Capture-MS), HSF1 (Affinity Capture-MS), HSF1 (Affinity Capture-MS), HSF1 (Affinity Capture-MS), HSF1 (Affinity Capture-MS), HSF1 (Affinity Capture-Western), HSF1 (Affinity Capture-Western), HSF1 (Affinity Capture-Western), HSF1 (Two-hybrid)

ESM2 similar proteins: A1L224, A2VD01, D3ZLB7, F6VAN0, G3V909, O02761, O35451, O43889, O77628, O88479, O94983, O97930, P01100, P01101, P01102, P0C0N8, P0C0N9, P11939, P12841, P18850, P20389, P38532, Q00613, Q08CW8, Q08DJ8, Q1LYG4, Q3SYZ3, Q502F0, Q56TN0, Q56TT7, Q5FVM5, Q5RCM9, Q5UEM7, Q5UEM8, Q61817, Q64210, Q66HA2, Q68CJ9, Q6QDP7, Q6ZPJ0

Diamond homologs: A0A1B0GTS1, A0A1B0GWH4, B7XIV9, C4V6H6, D0VYS2, G0SB31, G5EFT5, J9VHZ9, O14283, O49403, P10961, P22121, P22335, P22813, P38529, P38530, P38531, P38532, P38533, P41151, P41153, P41154, Q00613, Q02953, Q03933, Q08DJ8, Q10PR4, Q1HGE8, Q1PDN3, Q338B0, Q40152, Q4G112, Q5A4X5, Q5AQ33, Q5CZP2, Q5KMX8, Q5ND04, Q652B0, Q67TP9, Q6F388

SIGNOR signaling

29 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	HSF1	phosphorylation
PLK1	down-regulates	HSF1	phosphorylation
PRKCQ	up-regulates	HSF1	phosphorylation
MAPK8	“down-regulates activity”	HSF1	phosphorylation
HSF1	“up-regulates quantity by expression”	HSPA6	“transcriptional regulation”
HSBP1	“down-regulates activity”	HSF1	binding
DYRK2	“up-regulates activity”	HSF1	phosphorylation
AKT1	“up-regulates activity”	HSF1	phosphorylation
HIPK3	“up-regulates activity”	HSF1	phosphorylation
MAP2K1	“up-regulates activity”	HSF1	phosphorylation
MAPKAPK2	“down-regulates activity”	HSF1	phosphorylation
AKT2	“up-regulates activity”	HSF1	phosphorylation
GSK3B	down-regulates	HSF1	phosphorylation
MAPK3	down-regulates	HSF1	phosphorylation
CSNK2A2	up-regulates	HSF1	phosphorylation
CAMK2A	“up-regulates activity”	HSF1	phosphorylation
CSNK2A1	“up-regulates activity”	HSF1	phosphorylation
GSK3B	“down-regulates activity”	HSF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cellular response to heat stress	7	41.1×	6e-08
Regulation of HSF1-mediated heat shock response	10	20.8×	2e-08
PKR-mediated signaling	5	10.5×	4e-03
Death Receptor Signaling	5	10.4×	4e-03
G2/M Checkpoints	5	10.0×	4e-03
Cell Cycle Checkpoints	7	9.2×	6e-04
Clathrin-mediated endocytosis	7	8.9×	7e-04
Cell Cycle, Mitotic	12	8.6×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to heat	7	27.4×	4e-06
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	6	14.4×	7e-04
regulation of protein stability	6	8.6×	4e-03
protein folding	7	8.2×	2e-03
protein stabilization	10	7.6×	3e-04
cell division	10	5.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

95 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2487 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144291870:GCCCG:G	donor_gain	1.0000
8:144308904:A:AG	acceptor_gain	1.0000
8:144308904:AGAGC:A	acceptor_gain	1.0000
8:144308905:G:GG	acceptor_gain	1.0000
8:144308905:GA:G	acceptor_gain	1.0000
8:144308905:GAGC:G	acceptor_gain	1.0000
8:144308905:GAGCG:G	acceptor_gain	1.0000
8:144309010:CATGT:C	donor_gain	1.0000
8:144309011:ATGT:A	donor_gain	1.0000
8:144309013:GT:G	donor_gain	1.0000
8:144309015:G:GA	donor_loss	1.0000
8:144309015:G:GG	donor_gain	1.0000
8:144309016:TGAG:T	donor_loss	1.0000
8:144309448:T:G	acceptor_gain	1.0000
8:144309448:T:TA	acceptor_gain	1.0000
8:144309450:TGCA:T	acceptor_loss	1.0000
8:144309453:A:AG	acceptor_gain	1.0000
8:144309453:AGAT:A	acceptor_gain	1.0000
8:144309453:AGATG:A	acceptor_gain	1.0000
8:144309454:G:GA	acceptor_gain	1.0000
8:144309454:GA:G	acceptor_gain	1.0000
8:144309454:GAT:G	acceptor_gain	1.0000
8:144309454:GATG:G	acceptor_gain	1.0000
8:144309454:GATGG:G	acceptor_gain	1.0000
8:144309579:G:GT	donor_gain	1.0000
8:144309580:A:T	donor_gain	1.0000
8:144309587:CCAGT:C	donor_gain	1.0000
8:144309588:CAGT:C	donor_gain	1.0000
8:144309590:GT:G	donor_gain	1.0000
8:144309590:GTGTG:G	donor_loss	1.0000

AlphaMissense

3486 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144291809:T:C	F18L	1.000
8:144291810:T:C	F18S	1.000
8:144291810:T:G	F18C	1.000
8:144291811:C:A	F18L	1.000
8:144291811:C:G	F18L	1.000
8:144291813:T:C	L19P	1.000
8:144291818:A:G	K21E	1.000
8:144291820:G:C	K21N	1.000
8:144291820:G:T	K21N	1.000
8:144291822:T:C	L22P	1.000
8:144291831:T:A	L25H	1.000
8:144291831:T:C	L25P	1.000
8:144291861:T:A	I35N	1.000
8:144291866:T:A	W37R	1.000
8:144291866:T:C	W37R	1.000
8:144291868:G:C	W37C	1.000
8:144291868:G:T	W37C	1.000
8:144308918:T:C	F44L	1.000
8:144308919:T:C	F44S	1.000
8:144308920:C:A	F44L	1.000
8:144308920:C:G	F44L	1.000
8:144308925:T:A	V46E	1.000
8:144308942:T:C	F52L	1.000
8:144308943:T:C	F52S	1.000
8:144308943:T:G	F52C	1.000
8:144308944:T:A	F52L	1.000
8:144308944:T:G	F52L	1.000
8:144308946:C:A	A53D	1.000
8:144308958:T:A	L57Q	1.000
8:144308958:T:C	L57P	1.000

dbSNP variants (sampled 300 via entrez): RS1000290335 (8:144294665 T>C), RS1000388583 (8:144304148 G>A,C), RS1000414615 (8:144299250 T>C), RS1000797555 (8:144307878 T>C), RS1000828949 (8:144308035 A>G), RS1001075726 (8:144312492 C>T), RS1001344950 (8:144291123 C>G,T), RS1001404343 (8:144312291 A>G), RS1001418587 (8:144291971 A>G), RS1001500299 (8:144310092 C>A), RS1001507428 (8:144312719 C>G,T), RS1001934985 (8:144295632 C>T), RS1002068617 (8:144314637 G>A,C), RS1002081754 (8:144300296 A>G), RS1002154027 (8:144300436 C>G,T)

Disease associations

OMIM: gene MIM:140580 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004858_12	Dupuytren’s disease	5.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3988631 (PROTEIN FAMILY), CHEMBL5869 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,257 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2103840	DINACICLIB	3	2,257

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

63 potent at pChembl≥5 of 108 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.55	IC50	2.8	nM	CHEMBL4070633
8.55	IC50	2.818	nM	CHEMBL4070633
8.15	IC50	7	nM	DINACICLIB
7.92	IC50	12.02	nM	CHEMBL4063330
7.92	IC50	12	nM	CHEMBL4063330
7.85	IC50	14	nM	CHEMBL3975567
7.82	IC50	15	nM	CHEMBL3937369
7.73	IC50	18.62	nM	CHEMBL4087666
7.72	IC50	19	nM	CHEMBL4087666
7.58	IC50	26	nM	CHEMBL4102297
7.58	IC50	26.3	nM	CHEMBL4102297
7.55	IC50	28	nM	CHEMBL3911352
7.41	IC50	39	nM	CHEMBL3964729
7.40	IC50	39.81	nM	CHEMBL4087666
7.40	IC50	40	nM	CHEMBL4087666
7.35	IC50	45	nM	CHEMBL3972065
7.29	IC50	51.29	nM	CHEMBL4069552
7.29	IC50	51	nM	CHEMBL4069552
7.26	IC50	55	nM	CHEMBL3953713
7.24	IC50	57	nM	CHEMBL3928361
7.17	IC50	67.61	nM	CHEMBL4070633
7.17	IC50	68	nM	CHEMBL4070633
7.10	IC50	80	nM	CHEMBL3919811
6.94	IC50	114.8	nM	CHEMBL4070302
6.92	IC50	120	nM	CHEMBL4070302
6.78	IC50	165	nM	CHEMBL3983798
6.70	IC50	198	nM	CHEMBL3901185
6.66	IC50	220	nM	CHEMBL4096048
6.65	IC50	223.9	nM	CHEMBL4096048
6.53	IC50	295	nM	CHEMBL3900925
6.35	IC50	450	nM	CHEMBL3919459
6.35	IC50	446.7	nM	CHEMBL4077078
6.35	IC50	450	nM	CHEMBL4077078
6.21	IC50	610	nM	CHEMBL3946252
6.12	IC50	760	nM	CHEMBL3936187
6.12	IC50	750	nM	CHEMBL3967087
6.08	IC50	842	nM	CHEMBL3944589
6.05	IC50	884	nM	CHEMBL3955977
5.96	EC50	1100	nM	CELASTROL
5.92	IC50	1200	nM	CHEMBL3609826
5.89	EC50	1300	nM	CHEMBL550251
5.87	IC50	1350	nM	CHEMBL3923966
5.86	IC50	1380	nM	CHEMBL3947240
5.70	IC50	2000	nM	CHEMBL3905315
5.68	EC50	2100	nM	CHEMBL550249
5.63	IC50	2330	nM	CHEMBL3891011
5.60	EC50	2500	nM	CHEMBL558033
5.60	EC50	2500	nM	CHEMBL564316
5.60	EC50	2500	nM	CHEMBL559039
5.59	IC50	2570	nM	CHEMBL4099031

PubChem BioAssay actives

62 with measured affinity, of 374 total; 47 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434074: Inhibition of 17-AAG-induced HSF1 pathway in human U20S cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.0028	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1322658: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after 18 hrs by ELISA	ic50	0.0070	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]quinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.0120	uM
6-imidazo[4,5-b]pyridin-1-yl-N-[5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0140	uM
6-imidazo[4,5-b]pyridin-1-yl-N-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0150	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-2-(2-pyrrolidin-1-ylethoxy)quinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.0186	uM
2-(2-aminoethoxy)-N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]quinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.0260	uM
N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]-6-imidazo[4,5-b]pyridin-1-ylpyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0280	uM
N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]-6-(6-methylbenzimidazol-1-yl)pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0390	uM
6-(benzimidazol-1-yl)-N-[5-[[(2R)-1-methylpyrrolidin-2-yl]methoxy]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0450	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]isoquinoline-7-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.0510	uM
6-(benzimidazol-1-yl)-N-[5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0550	uM
6-(benzimidazol-1-yl)-N-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0570	uM
6-(benzimidazol-1-yl)-N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.0800	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-2-[2-(propanoylamino)ethoxy]quinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.1148	uM
6-(benzimidazol-1-yl)-N-[5-[3-(dimethylamino)propoxy]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.1650	uM
6-(benzimidazol-1-yl)-N-[5-[3-(dimethylamino)propyl]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.1980	uM
N-[5-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)-2-methylphenyl]-1,2,3,4-tetrahydroquinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.2200	uM
6-(benzimidazol-1-yl)-N-[5-(2-morpholin-4-ylethoxy)-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.2950	uM
N-[5-(3,4-dihydro-2H-chromene-7-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	0.4467	uM
6-(benzimidazol-1-yl)-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.4500	uM
6-(benzimidazol-1-yl)-N-[5-[4-(dimethylamino)piperidin-1-yl]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.6100	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperazine-1-carboxamide	1322658: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after 18 hrs by ELISA	ic50	0.7500	uM
N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]-6-imidazo[4,5-b]pyridin-3-ylpyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.7600	uM
6-(benzimidazol-1-yl)-N-pyridin-2-ylpyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.8420	uM
6-(benzimidazol-1-yl)-N-[5-(1-methylpiperidin-4-yl)oxy-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	0.8840	uM
(2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	1.1000	uM
2-N-(1H-indazol-5-yl)-6-N-methyl-3-nitropyridine-2,6-diamine	1242159: Inhibition of HSF1 (unknown origin) assessed as reduction in HSF1–mediated HSP transcription	ic50	1.2000	uM
3-(1,3-benzothiazol-2-yl)-6-methyl-1-(2-methylpropyl)pyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	1.3000	uM
6-(benzimidazol-1-yl)-N-[4-[2-(dimethylamino)ethoxy]phenyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	1.3500	uM
6-(benzimidazol-1-yl)-N-[5-[(2S)-2,4-dimethylpiperazin-1-yl]-2-pyridinyl]pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	1.3800	uM
2-[4-[[6-(benzimidazol-1-yl)pyrimidin-4-yl]amino]phenyl]ethanol	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	2.0000	uM
1-butyl-6-methyl-3-(1,3-thiazol-2-yl)pyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	2.1000	uM
N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]-6-indol-1-ylpyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	2.3300	uM
3-(1,3-benzothiazol-2-yl)-1-butyl-6-methylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	2.5000	uM
1-butyl-6-methyl-3-quinolin-2-ylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	2.5000	uM
3-(1,3-benzothiazol-2-yl)-6-methyl-1-(3-methylbutyl)pyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	2.5000	uM
N-[5-(3,4-dihydro-2H-chromene-6-carbonylamino)-2-methylphenyl]-2-methylquinoline-6-carboxamide	1434112: Inhibition of 17-AAG-induced HSF1 pathway in human SKOV3 cells assessed as reduction in HSP72 induction preincubated for 1 hr followed by 17-AAG addition measured after 18 hrs by ELISA	ic50	2.5704	uM
3-(1,3-benzothiazol-2-yl)-1-benzyl-6-methylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	4.1000	uM
N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]-6-(2-methylbenzimidazol-1-yl)pyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	4.2800	uM
4-[[3-[[3-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-oxopropyl]amino]-3-oxopropyl]carbamoyl]-2-(3-hydroxy-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid	1424680: Binding affinity to recombinant human HSF1 monomer expressed in Escherichia coli BL21 (DE3) after 15 mins by fluorescence polarization assay	ec50	4.5000	uM
1-ethyl-6-methyl-3-thiophen-2-ylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	5.1000	uM
N-[5-[2-(dimethylamino)ethoxy]-2-pyridinyl]-6-imidazol-1-ylpyrimidin-4-amine	1322649: Inhibition of 17AAG-induced HSF1-mediated HSP72 expression in human U2OS cells preincubated for 1 hr followed by 17AAG addition measured after overnight incubation by ArrayScan analysis	ic50	6.1500	uM
1-butyl-3-(1H-imidazol-2-yl)-6-methylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	7.7000	uM
1-butyl-6-methyl-3-(5-methylthiophen-2-yl)-4-oxidopyrimido[5,4-e][1,2,4]triazin-4-ium-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	8.6000	uM
1-butyl-6-methyl-3-(5-methylfuran-2-yl)pyrimido[5,4-e][1,2,4]triazine-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	9.9000	uM
1-butyl-6-methyl-3-(5-methylfuran-2-yl)-4-oxidopyrimido[5,4-e][1,2,4]triazin-4-ium-5,7-dione	428034: Amplification of HSF1 transcriptional activity in human heat shock-induced HeLa cells assessed as granule formation treated 1 hr before heat shock challenge measured after 2 hrs without recovery time by immunocytochemical staining	ec50	10.0000	uM

CTD chemical–gene interactions

212 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases reaction, increases expression, affects cotreatment, decreases reaction, affects reaction (+4 more)	8
Cadmium Chloride	decreases activity, decreases reaction, affects binding, increases reaction, decreases expression (+2 more)	5
Bortezomib	affects binding, increases reaction, increases activity, increases expression	4
Resveratrol	decreases phosphorylation, decreases reaction, decreases activity, decreases localization, decreases expression (+1 more)	4
Arsenic Trioxide	decreases reaction, increases phosphorylation, increases activity, increases cleavage, increases expression (+4 more)	4
Acetylcysteine	affects binding, increases reaction, decreases activity, decreases reaction, affects localization	3
Acrolein	affects cotreatment, increases oxidation, increases activity, increases abundance	3
Air Pollutants	increases oxidation, increases expression, affects cotreatment, increases abundance	3
Benzo(a)pyrene	affects activity, affects methylation, increases activity	3
Hydrogen Peroxide	increases activity, increases expression	3
Quercetin	decreases reaction, increases expression, decreases expression, increases response to substance	3
Silver Nitrate	affects binding, increases reaction, increases activity	3
Zinc	increases activity, affects binding, increases reaction	3
geldanamycin	increases activity, increases phosphorylation, affects binding, decreases reaction, increases reaction	2
bisphenol A	affects expression, increases phosphorylation	2
cadmium sulfate	affects binding, increases reaction, increases activity	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, increases reaction, increases activity	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	2
15-deoxy-delta(12,14)-prostaglandin J2	increases expression, increases activity, decreases reaction	2
tanespimycin	affects localization, increases expression, increases activity	2
N2-(1H-indazole-5-yl)-N6-methyl-3-nitropyridine-2,6-diamine	decreases reaction, increases expression, affects binding, increases reaction	2
Wortmannin	affects localization, decreases reaction, increases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Vehicle Emissions	affects localization, decreases reaction, increases activity	2
Cadmium	affects binding, increases reaction, increases activity	2
Formaldehyde	increases activity, increases phosphorylation	2
Indomethacin	increases activity	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Silver	affects binding, increases reaction, increases activity	2

ChEMBL screening assays

105 unique, capped per target: 105 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3881365	Binding	Activation of HSF in human HeLa cell clone 13B after 8 hrs by luciferase reporter gene assay	Cyclopentanone and cyclopentanone derivatives as potent activators of HSF-1

Cellosaurus cell lines

12 cell lines: 5 cancer cell line, 4 embryonic stem cell, 2 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3B7	SEES3-1V human HSF1, clone1	Embryonic stem cell	Male
CVCL_A3B8	SEES3-1V human HSF1, clone2	Embryonic stem cell	Male
CVCL_A3B9	SEES3-1V human HSF1, clone3	Embryonic stem cell	Male
CVCL_A4GX	SAM iPSC clone 1	Induced pluripotent stem cell	Female
CVCL_A4GY	SAM iPSC clone 2	Induced pluripotent stem cell	Female
CVCL_C9DX	HEK293T-CRISPRa	Transformed cell line	Female
CVCL_E7G6	H9-iCas9.SAM	Embryonic stem cell	Female
CVCL_E8FJ	HCC827(gFGFR1)	Cancer cell line	Female
CVCL_E8FK	PC-9(gFGFR1)	Cancer cell line	Male
CVCL_SR71	HAP1 HSF1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.