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
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.
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.
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.
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