Protein: Heat shock factor protein 1 (HSF 1) (Heat shock transcription factor 1) (HSTF 1) (P38532)
Organism: Mus musculus (Mouse)
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.
Subcellular location: Nucleus {ECO:0000269|PubMed:26159920}. Cytoplasm {ECO:0000269|PubMed:26159920}. Nucleus, nucleoplasm {ECO:0000250|UniProtKB:Q00613}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q00613}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q00613}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q00613}. Chromosome, centromere, kinetochore {ECO:0000250|UniProtKB:Q00613}. Note=The monomeric form is cytoplasmic in unstressed cells (PubMed:26159920). Predominantly nuclear protein in both unstressed and heat shocked cells. Translocates in the nucleus upon heat shock. Nucleocytoplasmic shuttling protein. Colocalizes with IER5 in the nucleus. Colocalizes with BAG3 to the nucleus upon heat stress. Localizes in subnuclear granules called nuclear stress bodies (nSBs) upon heat shock. Colocalizes with SYMPK and SUMO1 in nSBs upon heat shock. Colocalizes with PRKACA/PKA in the nucleus and nSBs upon heat shock. Relocalizes from the nucleus to the cytoplasm during the attenuation and recovery phase period of the heat shock response. Translocates in the cytoplasm in a YWHAE- and XPO1/CRM1-dependent manner. Together with histone H2AX, redistributed in discrete nuclear DNA damage-induced foci after ionizing radiation (IR). Colocalizes with calcium-responsive transactivator SS18L1 at kinetochore region on the mitotic chromosomes. Colocalizes with gamma tubulin at centrosome. Localizes at spindle pole in metaphase. Colocalizes with PLK1 at spindle poles during prometaphase. {ECO:0000250|UniProtKB:Q00613, ECO:0000269|PubMed:26159920}.
Sequence: MDLAVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKYFKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVTSVSTLKSEDIKIRQDSVTRLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHAQQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLSDSNSAHSVPKYGRQYSLEHVHGPGPYSAPSPAYSSSSLYSSDAVTSSGPIISDITELAPTSPLASPGRSIDERPLSSSTLVRVKQEPPSPPHSPRVLEASPGRPSSMDTPLSPTAFIDSILRESEPTPAASNTAPMDTTGAQAPALPTPSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLTSHGFSVDTSALLDLFSPSVTMPDMSLPDLDSSLASIQELLSPQEPPRPIEAENSNPDSGKQLVHYTAQPLFLLDPDAVDTGSSELPVLFELGESSYFSEGDDYTDDPTISLLTGTEPHKAKDPTVS
InterPro domains: - IPR000232: Heat shock factor (HSF)-type, DNA-binding (domain) [14-118]
- IPR036390: Winged helix DNA-binding domain superfamily (homologous_superfamily) [13-118]
- IPR010542: Vertebrate heat shock transcription factor, C-terminal domain (domain) [247-525]
- IPR036388: Winged helix-like DNA-binding domain superfamily (homologous_superfamily) [11-120]
Interaction partners: - Heat shock protein HSP 90-beta
- Heat shock protein HSP 90-alpha
- Heat shock 70 kDa protein 1B
- DnaJ homolog subfamily B member 1
- Heat shock cognate 71 kDa protein
- Heat shock 70 kDa protein 1A
- Elongation factor 1-alpha 1
- Elongation factor 1-alpha 2
- Transitional endoplasmic reticulum ATPase
- E3 ubiquitin-protein ligase CHIP
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:1901363 (heterocyclic compound binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0042802 (identical protein binding), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009058 (biosynthetic process), GO:0019222 (regulation of metabolic process), GO:0008283 (cell population proliferation), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0003008 (system process), GO:0070988 (demethylation), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051094 (positive regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0045597 (positive regulation of cell differentiation), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0006482 (protein demethylation), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0046483 (heterocycle metabolic process), GO:0048731 (system development), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0060255 (regulation of macromolecule metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:0042127 (regulation of cell population proliferation), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0050673 (epithelial cell proliferation), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0050877 (nervous system process), GO:0080090 (regulation of primary metabolic process), GO:0008284 (positive regulation of cell population proliferation), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0048880 (sensory system development), GO:0019438 (aromatic compound biosynthetic process), GO:0007423 (sensory organ development), GO:0050678 (regulation of epithelial cell proliferation), GO:0007600 (sensory perception), GO:0010468 (regulation of gene expression), GO:0050679 (positive regulation of epithelial cell proliferation), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0016577 (histone demethylation), GO:0036211 (protein modification process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0043412 (macromolecule modification), GO:0090304 (nucleic acid metabolic process), GO:0018130 (heterocycle biosynthetic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010467 (gene expression), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0070076 (histone lysine demethylation), GO:0016070 (RNA metabolic process), GO:0050953 (sensory perception of light stimulus), GO:0001654 (eye development), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0150063 (visual system development), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0008214 (protein dealkylation), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0032774 (RNA biosynthetic process), GO:0097659 (nucleic acid-templated transcription), GO:0016570 (histone modification), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045893 (positive regulation of DNA-templated transcription), GO:0007601 (visual perception), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0043010 (camera-type eye development), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006351 (DNA-templated transcription), GO:0045944 (positive regulation of transcription by RNA polymerase II), GO:0000122 (negative regulation of transcription by RNA polymerase II), GO:0006366 (transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0000785 (chromatin), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus), GO:0005694 (chromosome)