P38532 (HSF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heat shock factor protein 1
Short name=HSF 1

Alternative name(s):
Heat shock transcription factor 1
Short name=HSTF 1

Gene names

Name:

Hsf1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	525 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	Monomer By similarity. 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. Interacts with EEF1D at heat shock promoter elements (HSE) By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: Cytoplasmic during normal growth. On activation, translocates to nuclear stress granules. Colocalizes with SUMO1 in nuclear stress granules By similarity.
Post-translational modification	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 By similarity. 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 By similarity.
Sequence similarities	Belongs to the HSF family.

Ontologies

Keywords
Biological process	Stress response Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to heat Inferred from sequence or structural similarity. Source: UniProtKB embryonic placenta development Inferred from mutant phenotype PubMed 10545106. Source: MGI embryonic process involved in female pregnancy Inferred from mutant phenotype PubMed 10545106. Source: MGI female meiosis Inferred from mutant phenotype PubMed 21690297. Source: MGI negative regulation of cell proliferation Inferred from genetic interaction PubMed 15483628. Source: MGI negative regulation of tumor necrosis factor production Inferred from mutant phenotype PubMed 10545106. Source: MGI positive regulation of multicellular organism growth Inferred from mutant phenotype PubMed 10545106. Source: MGI protein phosphorylation Inferred from direct assay PubMed 18755693. Source: MGI regulation of spindle checkpoint Inferred from mutant phenotype PubMed 21690297. Source: MGI response to lipopolysaccharide Inferred from mutant phenotype PubMed 10545106. Source: MGI spermatogenesis Inferred from genetic interaction PubMed 14994269. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 11032181PubMed 14766729. Source: MGI pronucleus Inferred from direct assay PubMed 14766729. Source: MGI protein complex Inferred from physical interaction PubMed 17785525. Source: MGI
Molecular_function	chromatin binding Inferred from direct assay PubMed 21690297. Source: MGI sequence-specific DNA binding Inferred from direct assay PubMed 18755693. Source: MGI sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: P38532-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P38532-2)

The sequence of this isoform differs from the canonical sequence as follows:
     413-434: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 525	525	Heat shock factor protein 1		PRO_0000124568
Regions
	DNA binding	15 – 120	106	By similarity
	Region	130 – 203	74	Hydrophobic repeat HR-A/B
	Region	221 – 310	90	Regulatory domain
	Region	367 – 525	159	Transactivation domain
	Region	380 – 405	26	Hydrophobic repeat HR-C
Amino acid modifications
	Modified residue	121	1	Phosphoserine; by MAPKAPK2 By similarity
	Modified residue	142	1	Phosphothreonine; by CK2 By similarity
	Modified residue	230	1	Phosphoserine By similarity
	Modified residue	292	1	Phosphoserine By similarity
	Modified residue	303	1	Phosphoserine Ref.4
	Modified residue	307	1	Phosphoserine Ref.4
	Modified residue	314	1	Phosphoserine By similarity
	Modified residue	323	1	Phosphothreonine By similarity
	Modified residue	326	1	Phosphoserine By similarity
	Modified residue	345	1	Phosphoserine By similarity
	Modified residue	415	1	Phosphoserine By similarity
	Modified residue	440	1	Phosphoserine By similarity
	Cross-link	298		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Alternative sequence	413 – 434	22	Missing in isoform 1.		VSP_002416

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified August 30, 2002. Version 2. Checksum: DCB6418FC12F5F43	FASTA	525	57,223
	10 20 30 40 50 60 MDLAVGPGAA GPSNVPAFLT KLWTLVSDPD TDALICWSPS GNSFHVFDQG QFAKEVLPKY 70 80 90 100 110 120 FKHNNMASFV RQLNMYGFRK VVHIEQGGLV KPERDDTEFQ HPCFLRGQEQ LLENIKRKVT 130 140 150 160 170 180 SVSTLKSEDI KIRQDSVTRL LTDVQLMKGK QECMDSKLLA MKHENEALWR EVASLRQKHA 190 200 210 220 230 240 QQQKVVNKLI QFLISLVQSN RILGVKRKIP LMLSDSNSAH SVPKYGRQYS LEHVHGPGPY 250 260 270 280 290 300 SAPSPAYSSS SLYSSDAVTS SGPIISDITE LAPTSPLASP GRSIDERPLS SSTLVRVKQE 310 320 330 340 350 360 PPSPPHSPRV LEASPGRPSS MDTPLSPTAF IDSILRESEP TPAASNTAPM DTTGAQAPAL 370 380 390 400 410 420 PTPSTPEKCL SVACLDKNEL SDHLDAMDSN LDNLQTMLTS HGFSVDTSAL LDLFSPSVTM 430 440 450 460 470 480 PDMSLPDLDS SLASIQELLS PQEPPRPIEA ENSNPDSGKQ LVHYTAQPLF LLDPDAVDTG 490 500 510 520 SSELPVLFEL GESSYFSEGD DYTDDPTISL LTGTEPHKAK DPTVS
	Isoform 1 [UniParc]. Checksum: 0795ABB6FA169F7B	FASTA	503	54,931
	10 20 30 40 50 60 MDLAVGPGAA GPSNVPAFLT KLWTLVSDPD TDALICWSPS GNSFHVFDQG QFAKEVLPKY 70 80 90 100 110 120 FKHNNMASFV RQLNMYGFRK VVHIEQGGLV KPERDDTEFQ HPCFLRGQEQ LLENIKRKVT 130 140 150 160 170 180 SVSTLKSEDI KIRQDSVTRL LTDVQLMKGK QECMDSKLLA MKHENEALWR EVASLRQKHA 190 200 210 220 230 240 QQQKVVNKLI QFLISLVQSN RILGVKRKIP LMLSDSNSAH SVPKYGRQYS LEHVHGPGPY 250 260 270 280 290 300 SAPSPAYSSS SLYSSDAVTS SGPIISDITE LAPTSPLASP GRSIDERPLS SSTLVRVKQE 310 320 330 340 350 360 PPSPPHSPRV LEASPGRPSS MDTPLSPTAF IDSILRESEP TPAASNTAPM DTTGAQAPAL 370 380 390 400 410 420 PTPSTPEKCL SVACLDKNEL SDHLDAMDSN LDNLQTMLTS HGFSVDTSAL LDIQELLSPQ 430 440 450 460 470 480 EPPRPIEAEN SNPDSGKQLV HYTAQPLFLL DPDAVDTGSS ELPVLFELGE SSYFSEGDDY 490 500 TDDPTISLLT GTEPHKAKDP TVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of two mouse heat shock factors with distinct inducible and constitutive DNA-binding ability." Sarge K.D., Zimarino V., Holm K., Wu C., Morimoto R.I. Genes Dev. 5:1902-1911(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: WEHI-3.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	"Structural organization and promoter analysis of murine heat shock transcription factor-1 gene." Zhang Y., Koushik S., Dai R., Mivechi N.F. J. Biol. Chem. 273:32514-32521(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 40-525 (ISOFORM 2). Strain: 129/SvJ. Tissue: Liver.
[4]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303 AND SER-307, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X61753 mRNA. Translation: CAA43892.1. BC013716 mRNA. Translation: AAH13716.1. AF059275 Genomic DNA. Translation: AAC80425.1.
IPI	IPI00132662. IPI00230223.
PIR	A40583.
RefSeq	NP_032322.1. NM_008296.2.
UniGene	Mm.347444.
3D structure databases
ProteinModelPortal	P38532.
SMR	P38532. Positions 10-123.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000023215.
PTM databases
PhosphoSite	P38532.
Proteomic databases
PRIDE	P38532.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000072838; ENSMUSP00000072617; ENSMUSG00000022556.
GeneID	15499.
KEGG	mmu:15499.
UCSC	uc007wkh.1. mouse.
Organism-specific databases
CTD	3297.
MGI	MGI:96238. Hsf1.
Phylogenomic databases
eggNOG	COG5169.
GeneTree	ENSGT00390000001182.
HOGENOM	HOG000253917.
HOVERGEN	HBG005999.
InParanoid	P38532.
KO	K09414.
OMA	SPLVRVK.
OrthoDB	EOG4VMFFN.
Gene expression databases
ArrayExpress	P38532.
Bgee	P38532.
CleanEx	MM_HSF1.
Genevestigator	P38532.
GermOnline	ENSMUSG00000022556. Mus musculus.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR027072. HSF1. IPR000232. HSF_DNA-bd. IPR010542. Vert_HS_TF. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
PANTHER	PTHR10015:SF42. PTHR10015:SF42. 1 hit.
Pfam	PF00447. HSF_DNA-bind. 1 hit. PF06546. Vert_HS_TF. 1 hit. [Graphical view]
PRINTS	PR00056. HSFDOMAIN.
SMART	SM00415. HSF. 1 hit. [Graphical view]
PROSITE	PS00434. HSF_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5313.
NextBio	288390.
SOURCE	Search...

Entry information

Entry name

HSF1_MOUSE

Accession

Primary (citable) accession number: P38532
Secondary accession number(s): O70462

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	August 30, 2002
Last modified:	May 1, 2013
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program