Sequence-Function

Using PROSITE I discovered two sequence signatures within the Kluyveromyces lactis Heat Shock Factor. The first domain is designated the HSF_DOMAIN because it occurs in all proteins known to function as heat shock transcription factors and is required for the binding of HSF to the heat shock response elements. Two other yeast proteins not involved in the heat shock response, Yeast SFL1 a protein involved in cell surface assembly and Yeast transcription factor SKN7 which binds to the promoter elements SCB and MCB, also contain this pattern suggesting that a similar mechanism of DNA binding may have been coopted by other transcription factors. The consensus pattern is:

L-x(3)-[FY]-K-H-x-N-x-[STAN]-S-F-[LIVM]-R-Q-L-[NH]-x-Y-x-[FYW]-[RKH]-K- [LIVM].

This motif has been found in the following proteins:

HSF1_ARATH (P41151), HSF1_CHICK (P38529), HSF1_HUMAN (Q00613), 
HSF1_MOUSE (P38532), HSF2_CHICK (P38530), HSF2_HUMAN (Q03933), 
HSF2_LYCPE (P22335), HSF2_MOUSE (P38533), HSF3_CHICK (P38531), 
HSF3_LYCPE (P41152), HSF8_LYCPE (P41153), HSF_DROME  (P22813), 
HSF_KLULA  (P22121), HSF_SCHPO  (Q02953), HSF_XENLA  (P41154), 
HSF_YEAST  (P10961), MGA1_YEAST (P53050), SFL1_YEAST (P20134), 
SKN7_YEAST (P38889)

The second motif found by PROSITE is a nuclear localization signal (NLS) which is required for protein translocation into the nucleus. The one found in HSF is somewhat different from most because it is seperated into two regions. This 'bipartite nuclear targeting sequence' is defined by three parameters:

(1) Two adjacent basic amino acids (Arg or Lys).
(2) A spacer region of any 10 residues.
(3) At least three basic residues (Arg or Lys) in the five positions after the spacer region.

Outside of these two domains no significant similarity was found between the HSF sequence and any of the sequence motifs in PROSITE.