[3] These activators bind specifically to Heat Shock sequence Elements (HSE) throughout the genome[4] whose consensus-sequence is a tandem array of three oppositely oriented "AGAAN" motifs or a degenerate version thereof.

Under non-stressed conditions, Drosophila HSF is a nuclear-localized unbound monomer, whereas heat shock activation results in trimerization and binding to the HSE.

[7] Its function is not only critical to overcome the proteotoxic effects of thermal stress, but also needed for proper animal development and the overall survival of cancer cells.

[10] Point mutations in these regions result in disruption of cellular localisation, rendering the protein constitutively nuclear in humans.

[5] Two sequences flanking the N-terminal zippers fit the consensus of a bi-partite nuclear localization signal (NLS).