HSF

heat shock factor

• SMART accession number: SM00415
• Interpro abstract (IPR000232): Heat shock factor (HSF) is a transcriptional activator of heat shock genes [(PUBMED:2257625)]: it binds specifically to heat shock promoter elements, which are palindromic sequences rich with repetitive purine and pyrimidine motifs [(PUBMED:2257625)]. Under normal conditions, HSF is a homo-trimeric cytoplasmic protein, but heat shock activation results in relocalisation to the nucleus [(PUBMED:1871105)]. Each HSF monomer contains one C-terminal and three N-terminal leucine zipper repeats [(PUBMED:1871106)]. Point mutations in these regions result in disruption of cellular localisation, rendering the protein constitutively nuclear [(PUBMED:1871105)]. Two sequences flanking the N-terminal zippers fit the consensus of a bi- partite nuclear localisation signal (NLS). Interaction between the N- and C-terminal zippers may result in a structure that masks the NLS sequences: following activation of HSF, these may then be unmasked, resulting in relocalisation of the protein to the nucleus [(PUBMED:1871106)]. The DNA-binding component of HSF lies to the N terminus of the first NLS region, and is referred to as the HSF domain.
• GO process: regulation of transcription, DNA-dependent (GO:0006355)
• GO component: nucleus (GO:0005634)
• GO function: sequence-specific DNA binding (GO:0043565), sequence-specific DNA binding transcription factor activity (GO:0003700)

There are 1082 HSF domains in 1076 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Binding / catalysis: DNA-binding

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Harrison CJ, Bohm AA, Nelson HC
• Crystal structure of the DNA binding domain of the heat shock transcription factor.
• Science. 1994; 263: 224-7

The structure of the DNA binding domain, determined at 1.8 angstrom resolution, contains a three-helix bundle that is capped by a four-stranded antiparallel beta sheet. This structure is a variant of the helix-turn-helix motif, typified by catabolite activator protein. In the heat shock transcription factor, the first helix of the motif (alpha 2) has an alpha-helical bulge and a proline-induced kink. The angle between the two helices of the motif (alpha 2 and alpha 3) is about 20 degrees smaller than the average for canonical helix-turn-helix proteins. Nevertheless, the relative positions of the first and third helices of the bundle (alpha 1 and alpha 3) are conserved. It is proposed here that the first helix of the three-helix bundle be considered a component of the helix-turn-helix motif.

• Sorger PK
• Heat shock factor and the heat shock response.
• Cell. 1991; 65: 363-6

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
100.00	map02020	Two-component system - General

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with HSF domain which could be assigned to a KEGG orthologous group, and not all proteins containing HSF domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of HSF domains in PDB

PDB code	Title
1fbq	Heat shock transcription factor dna binding domain containing the p237k mutation
1fbs	Heat shock transcription factor dna binding domain containing the p237a mutation
1fbu	Heat shock transcription factor dna binding domain
1fyk	Serendipitous crystal structure containing the heat shock transcription factor's dna binding domain and cognate dna that is translationally disordered
1fyl	Serendipitous crystal structure containing the heat shock transcription factor's dna binding domain and cognate dna in a head-to-head orientation
1fym	Serendipitous crystal structure containing the heat shock transcription factor's dna binding domain and cognate dna in a tail-to-tail orientation
1hks	Solution structure of the dna-binding domain of drosophila heat shock transcription factor
1hkt	Solution structure of the dna-binding domain of drosophila heat shock transcription factor
2hts	Crystal structure of the dna binding domain of the heat shock transcription factor
3hsf	Heat shock transcription factor (hsf)
3hts	Heat shock transcription factor/dna complex

Links (links to other resources describing this domain)

• PFAM: HSF_DNA-bind
• INTERPRO: IPR000232
• PROSITE: HSF_DOMAIN