Human Gene HSF1 (ENST00000528838.6) from GENCODE V44
  Description: Homo sapiens heat shock transcription factor 1 (HSF1), mRNA. (from RefSeq NM_005526)
RefSeq Summary (NM_005526): 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. [provided by RefSeq, Jul 2017].
Gencode Transcript: ENST00000528838.6
Gencode Gene: ENSG00000185122.11
Transcript (Including UTRs)
   Position: hg38 chr8:144,291,604-144,314,720 Size: 23,117 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg38 chr8:144,291,758-144,314,330 Size: 22,573 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:144,291,604-144,314,720)mRNA (may differ from genome)Protein (529 aa)
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BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: HSF1_HUMAN
DESCRIPTION: RecName: Full=Heat shock factor protein 1; Short=HSF 1; AltName: Full=Heat shock transcription factor 1; Short=HSTF 1;
FUNCTION: DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. In higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked.
SUBUNIT: Monomer. Under normal conditions, interacts with HSP90AA1 in the HSP90 multichaperone complex; the interaction prevents trimerization and activation of HSF1. On activation by heat-stress or by other factors such as metal ions, HSF1 is released from the complex, homotrimerizes, is hyperphosphorylated and translocated to the nucleus where, subsequently, it can activate transcription. Binds the complex through the regulatory domain. Interacts with SYMPK and CSTF2 in heat-stressed cells. Interacts with FKBP4 in the HSP90 multichaperone complex; the interaction is independent of the phosphorylation state of HSF1. Interacts with MAPKAPK2.
INTERACTION: P49137:MAPKAPK2; NbExp=5; IntAct=EBI-719620, EBI-993299;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic during normal growth. On activation, translocates to nuclear stress granules. Colocalizes with SUMO1 in nuclear stress granules.
DOMAIN: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
PTM: Phosphorylated on multiple serine residues, a subset of which are involved in stress-related regulation of transcription activation. Constitutive phosphorylation represses transcriptional activity at normal temperatures. Levels increase on specific residues heat-shock and enhance HSF1 transactivation activity. Phosphorylation on Ser-307 derepresses activation on heat-stress and in combination with Ser-303 phosphorylation appears to be involved in recovery after heat-stress. Phosphorylated on Ser-230 by CAMK2, in vitro. Cadmium also enhances phosphorylation at this site. Phosphorylation on Ser-303 is a prerequisite for HSF1 sumoylation. Phosphorylation on Ser-121 inhibits transactivation and promotes HSP90 binding. Phosphorylation on Thr-142 also mediates transcriptional activity induced by heat.
PTM: Sumoylated with SUMO1 and SUMO2 on heat-shock. Heat-inducible sumoylation occurs after 15 min of heat-shock, after which levels decrease and at 4 hours, levels return to control levels. Sumoylation has no effect on HSE binding nor on transcriptional activity. Phosphorylation on Ser-303 is a prerequisite for sumoylation.
SIMILARITY: Belongs to the HSF family.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: HSF1
Diseases sorted by gene-association score: synucleinopathy (3), amyotrophic lateral sclerosis 1 (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 78.70 RPKM in Testis
Total median expression: 1358.78 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -80.10154-0.520 Picture PostScript Text
3' UTR -155.20390-0.398 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000232 - HSF_DNA-bd
IPR010542 - Vert_HS_TF
IPR011991 - WHTH_trsnscrt_rep_DNA-bd

Pfam Domains:
PF00447 - HSF-type DNA-binding
PF06546 - Vertebrate heat shock transcription factor

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2LDU - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q00613
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001162 RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0019901 protein kinase binding
GO:0031072 heat shock protein binding
GO:0031490 chromatin DNA binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding
GO:0043621 protein self-association
GO:0046982 protein heterodimerization activity
GO:0051879 Hsp90 protein binding
GO:0061770 translation elongation factor binding
GO:0097677 STAT family protein binding
GO:0098847 sequence-specific single stranded DNA binding
GO:1990841 promoter-specific chromatin binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000165 MAPK cascade
GO:0001701 in utero embryonic development
GO:0001892 embryonic placenta development
GO:0006281 DNA repair
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006397 mRNA processing
GO:0006468 protein phosphorylation
GO:0006952 defense response
GO:0006974 cellular response to DNA damage stimulus
GO:0007143 female meiotic division
GO:0007283 spermatogenesis
GO:0007584 response to nutrient
GO:0008284 positive regulation of cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0009299 mRNA transcription
GO:0009408 response to heat
GO:0010243 response to organonitrogen compound
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
GO:0014070 response to organic cyclic compound
GO:0014823 response to activity
GO:0032355 response to estradiol
GO:0032496 response to lipopolysaccharide
GO:0032720 negative regulation of tumor necrosis factor production
GO:0033574 response to testosterone
GO:0034605 cellular response to heat
GO:0034620 cellular response to unfolded protein
GO:0034622 cellular macromolecular complex assembly
GO:0035690 cellular response to drug
GO:0035865 cellular response to potassium ion
GO:0040018 positive regulation of multicellular organism growth
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0043200 response to amino acid
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043497 regulation of protein heterodimerization activity
GO:0045931 positive regulation of mitotic cell cycle
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051028 mRNA transport
GO:0051260 protein homooligomerization
GO:0060136 embryonic process involved in female pregnancy
GO:0061408 positive regulation of transcription from RNA polymerase II promoter in response to heat stress
GO:0070207 protein homotrimerization
GO:0070301 cellular response to hydrogen peroxide
GO:0071222 cellular response to lipopolysaccharide
GO:0071230 cellular response to amino acid stimulus
GO:0071276 cellular response to cadmium ion
GO:0071280 cellular response to copper ion
GO:0071392 cellular response to estradiol stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0071478 cellular response to radiation
GO:0071480 cellular response to gamma radiation
GO:0072738 cellular response to diamide
GO:0090084 negative regulation of inclusion body assembly
GO:0090261 positive regulation of inclusion body assembly
GO:1900034 regulation of cellular response to heat
GO:1900365 positive regulation of mRNA polyadenylation
GO:1901215 negative regulation of neuron death
GO:1901652 response to peptide
GO:1902512 positive regulation of apoptotic DNA fragmentation
GO:1903936 cellular response to sodium arsenite
GO:1904385 cellular response to angiotensin
GO:1904528 positive regulation of microtubule binding
GO:1904843 cellular response to nitroglycerin
GO:1904845 cellular response to L-glutamine
GO:1990910 response to hypobaric hypoxia
GO:1990911 response to psychosocial stress
GO:2001033 negative regulation of double-strand break repair via nonhomologous end joining

Cellular Component:
GO:0000775 chromosome, centromeric region
GO:0000776 kinetochore
GO:0000777 condensed chromosome kinetochore
GO:0000791 euchromatin
GO:0000792 heterochromatin
GO:0000922 spindle pole
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0016605 PML body
GO:0032991 macromolecular complex
GO:0045120 pronucleus
GO:0048471 perinuclear region of cytoplasm
GO:0097165 nuclear stress granule
GO:0097431 mitotic spindle pole
GO:1990904 ribonucleoprotein complex


-  Descriptions from all associated GenBank mRNAs
  M64673 - Human heat shock factor 1 (TCF5) mRNA, complete cds.
AK222497 - Homo sapiens mRNA for heat shock transcription factor 1 variant, clone: adSE00346.
AK290975 - Homo sapiens cDNA FLJ75130 complete cds, highly similar to Homo sapiens heat shock transcription factor 1 (HSF1), mRNA.
BC014638 - Homo sapiens heat shock transcription factor 1, mRNA (cDNA clone MGC:1407 IMAGE:3528599), complete cds.
AB463721 - Synthetic construct DNA, clone: pF1KB7811, Homo sapiens HSF1 gene for heat shock transcription factor 1, without stop codon, in Flexi system.
DQ893859 - Synthetic construct Homo sapiens clone IMAGE:100008319; FLH165021.01L; RZPDo839E11157D heat shock transcription factor 1 (HSF1) gene, encodes complete protein.
KJ891400 - Synthetic construct Homo sapiens clone ccsbBroadEn_00794 HSF1 gene, encodes complete protein.
BT007351 - Homo sapiens heat shock transcription factor 1 mRNA, complete cds.
AK125467 - Homo sapiens cDNA FLJ43478 fis, clone OCBBF3000323, highly similar to HEAT SHOCK FACTOR PROTEIN 1.
AK300205 - Homo sapiens cDNA FLJ56244 complete cds, highly similar to Heat shock factor protein 1.
JD256477 - Sequence 237501 from Patent EP1572962.
JD559266 - Sequence 540290 from Patent EP1572962.
DQ574423 - Homo sapiens piRNA piR-42535, complete sequence.
AK054762 - Homo sapiens cDNA FLJ30200 fis, clone BRACE2001455, highly similar to HEAT SHOCK FACTOR PROTEIN 1.
AF299094 - Homo sapiens heat shock transcription factor 1 mRNA, partial cds.
AK126580 - Homo sapiens cDNA FLJ44617 fis, clone BRACE2012947.
JD044276 - Sequence 25300 from Patent EP1572962.
JD466415 - Sequence 447439 from Patent EP1572962.
JD104867 - Sequence 85891 from Patent EP1572962.
JD365650 - Sequence 346674 from Patent EP1572962.
JD229650 - Sequence 210674 from Patent EP1572962.
JD349097 - Sequence 330121 from Patent EP1572962.
JD219805 - Sequence 200829 from Patent EP1572962.
JD099651 - Sequence 80675 from Patent EP1572962.
JD455724 - Sequence 436748 from Patent EP1572962.
JD097652 - Sequence 78676 from Patent EP1572962.
JD469780 - Sequence 450804 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q00613 (Reactome details) participates in the following event(s):

R-HSA-3371435 Constitutive phosphorylation by GSK3
R-HSA-3371531 Constitutive phosphorylation by pERK1/2
R-HSA-3371591 Trimerization of cytosolic HSF1
R-HSA-4793911 MAPKAPK2 phosphorylates HSF1
R-HSA-3371586 Dissociation of cytosolic HSF1:HSP90 complex
R-HSA-5324632 Dissociation of cytosolic HSF1:HSP90:HDAC6:PTGES3 upon sensing protein aggregates
R-HSA-4793925 p-S303,307-HSF1 binds YWHAE (14-3-3)
R-HSA-5082391 Trimerization of HSF1 in the nucleus
R-HSA-5082409 Dissociation of HSF1:HSP90 complex in the nucleus
R-HSA-3371582 HSBP1 binds HSF1 trimer
R-HSA-4793819 HSF1 trimer binds HSE on the target gene
R-HSA-5082387 Phosphorylation of HSF1 at Ser230 induces transactivation
R-HSA-5082405 Phosphorylation of HSF1 at Ser326 induces transactivation
R-HSA-5324617 HSP90:FKBP4:PTGES3 binds HSF1 trimer
R-HSA-5333051 RPA1 binds HSF1
R-HSA-5082384 HSP70:DNAJB1 binds HSF1
R-HSA-5082369 Acetylated HSF1 dissociates from DNA
R-HSA-3371518 SIRT1 binds to HSF1
R-HSA-3371554 HSF1 acetylation at Lys80
R-HSA-3371467 SIRT1 deacetylates HSF1
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-3371556 Cellular response to heat stress
R-HSA-2262752 Cellular responses to stress
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: A8K4L0, A8MW26, ENST00000528838.1, ENST00000528838.2, ENST00000528838.3, ENST00000528838.4, ENST00000528838.5, HSF1_HUMAN, HSTF1, NM_005526, Q00613, Q53XT4, uc003zbt.1, uc003zbt.2, uc003zbt.3, uc003zbt.4, uc003zbt.5, uc003zbt.6
UCSC ID: ENST00000528838.6
RefSeq Accession: NM_005526
Protein: Q00613 (aka HSF1_HUMAN)
CCDS: CCDS6419.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.