Overview
| Uniprot ID | Q00613 |
|---|
| Protein Name | Heat shock factor protein 1 |
|---|
| Gene Name | HSF1 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 224 |
GSAHSMPKYSRQFSL |
Function
Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage (PubMed:11447121, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:18451878, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7760831, PubMed:8940068, PubMed:8946918, PubMed:9121459, PubMed:9341107, PubMed:9499401, PubMed:9535852, PubMed:9727490). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:11583998, PubMed:16278218, PubMed:9727490). Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes (PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7935471, PubMed:8455624, PubMed:8940068, PubMed:9499401, PubMed:9727490). Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival (PubMed:18451878). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock gene promoters (PubMed:25963659). Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 (PubMed:34723967). Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells (PubMed:9341107). Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic progression (PubMed:18794143). Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner (PubMed:26359349). Involved in stress-induced cancer cell proliferation in a IER5-dependent manner (PubMed:26754925)
Protein Sequence
10
MDLPVGPGAA
20
GPSNVPAFLT
30
KLWTLVSDPD
40
TDALICWSPS
50
GNSFHVFDQG
60
QFAKEVLPKY
70
FKHNNMASFV
80
RQLNMYGFRK
90
VVHIEQGGLV
100
KPERDDTEFQ
110
HPCFLRGQEQ
120
LLENIKRKVT
130
SVSTLKSEDI
140
KIRQDSVTKL
150
LTDVQLMKGK
160
QECMDSKLLA
170
MKHENEALWR
180
EVASLRQKHA
190
QQQKVVNKLI
200
QFLISLVQSN
210
RILGVKRKIP
220
LMLNDSGSAH
230
SMPKYSRQFS
240
LEHVHGSGPY
250
SAPSPAYSSS
260
SLYAPDAVAS
270
SGPIISDITE
280
LAPASPMASP
290
GGSIDERPLS
300
SSPLVRVKEE
310
PPSPPQSPRV
320
EEASPGRPSS
330
VDTLLSPTAL
340
IDSILRESEP
350
APASVTALTD
360
ARGHTDTEGR
370
PPSPPPTSTP
380
EKCLSVACLD
390
KNELSDHLDA
400
MDSNLDNLQT
410
MLSSHGFSVD
420
TSALLDLFSP
430
SVTVPDMSLP
440
DLDSSLASIQ
450
ELLSPQEPPR
460
PPEAENSSPD
470
SGKQLVHYTA
480
QPLFLLDPGS
490
VDTGSNDLPV
500
LFELGEGSYF
510
SEGDGFAEDP
520
TISLLTGSEP
PKAKDPTVS
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005813 |
centrosome |
| Cellular Component |
GO:0000785 |
chromatin |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0000776 |
kinetochore |
| Cellular Component |
GO:0097431 |
mitotic spindle pole |
| Cellular Component |
GO:0097165 |
nuclear stress granule |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0048471 |
perinuclear region of cytoplasm |
| Cellular Component |
GO:0016605 |
PML body |
| Cellular Component |
GO:0045120 |
pronucleus |
| Cellular Component |
GO:0101031 |
protein folding chaperone complex |
| Cellular Component |
GO:1990904 |
ribonucleoprotein complex |
| Molecular Function |
GO:0031490 |
chromatin DNA binding |
| Molecular Function |
GO:0003677 |
DNA binding |
| Molecular Function |
GO:0001228 |
DNA-binding transcription activator activity, RNA polymerase II-specific |
| Molecular Function |
GO:0003700 |
DNA-binding transcription factor activity |
| Molecular Function |
GO:0000981 |
DNA-binding transcription factor activity, RNA polymerase II-specific |
| Molecular Function |
GO:0001227 |
DNA-binding transcription repressor activity, RNA polymerase II-specific |
| Molecular Function |
GO:0140296 |
general transcription initiation factor binding |
| Molecular Function |
GO:0031072 |
heat shock protein binding |
| Molecular Function |
GO:0051879 |
Hsp90 protein binding |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0046982 |
protein heterodimerization activity |
| Molecular Function |
GO:0019901 |
protein kinase binding |
| Molecular Function |
GO:0000978 |
RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| Molecular Function |
GO:0001162 |
RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding |
| Molecular Function |
GO:0043565 |
sequence-specific DNA binding |
| Molecular Function |
GO:1990837 |
sequence-specific double-stranded DNA binding |
| Molecular Function |
GO:0000976 |
transcription cis-regulatory region binding |
| Molecular Function |
GO:0061770 |
translation elongation factor binding |
| Biological Process |
GO:0071276 |
cellular response to cadmium ion |
| Biological Process |
GO:0071280 |
cellular response to copper ion |
| Biological Process |
GO:0072738 |
cellular response to diamide |
| Biological Process |
GO:0071480 |
cellular response to gamma radiation |
| Biological Process |
GO:0034605 |
cellular response to heat |
| Biological Process |
GO:1903936 |
cellular response to sodium arsenite |
| Biological Process |
GO:0034620 |
cellular response to unfolded protein |
| Biological Process |
GO:0006281 |
DNA repair |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0000165 |
MAPK cascade |
| Biological Process |
GO:0006397 |
mRNA processing |
| Biological Process |
GO:0051028 |
mRNA transport |
| Biological Process |
GO:2001033 |
negative regulation of double-strand break repair via nonhomologous end joining |
| Biological Process |
GO:0031333 |
negative regulation of protein-containing complex assembly |
| Biological Process |
GO:0000122 |
negative regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0120162 |
positive regulation of cold-induced thermogenesis |
| Biological Process |
GO:0010628 |
positive regulation of gene expression |
| Biological Process |
GO:0045651 |
positive regulation of macrophage differentiation |
| Biological Process |
GO:0045931 |
positive regulation of mitotic cell cycle |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0065003 |
protein-containing complex assembly |
| Biological Process |
GO:1900034 |
regulation of cellular response to heat |
| Biological Process |
GO:0006357 |
regulation of transcription by RNA polymerase II |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.