PROSITE documentation PDOC00564

Fork head domain signatures and profile

It has been shown [1] that some eukaryotic transcription factors contain a conserved domain of about 100 amino-acid residues, called the fork head domain (but also known as a "winged helix"), which is involved in DNA-binding [2]. Proteins known to contain this domain are listed below.

• Drosophila fork head protein (fkh). Fkh is probably a transcription factor that regulates the expression of genes involved in terminal development.
• Drosophila protein crocodile (gene croc) [3], which is required for the establishment of head structures.
• Drosophila proteins FD2, FD3, FD4, and FD5.
• Drosophila proteins sloppy paired 1 and 2 (slp1 and slp2) involved in segmentation.
• Bombyx mori silk gland factor-1 (SGF-1) which regulates transcription of the sericim-1 gene.
• Mammalian transcriptional activators HNF-3-α, -β, and -γ. The HNF-3 proteins interact with the cis-acting regulatory regions of a number of liver genes.
• Mammalian interleukin-enhancer binding factor (ILF). ILF binds to the purine-rich NFAT-like motifs in the HIV-1 LTR and the interleukin-2 promoter. ILF may be involved in both positive and negative regulation of important viral and cellular promoter elements.
• Mammalian transcription factor BF-1 which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.
• Human HTLF, a protein that binds to the purine-rich region in human T-cell leukemia virus long terminal repeat (HTLV-I LTR).
• Mammalian transcription factors FREAC-1 (FKHL5, HFH-8), FREAC-2 (FKHL6), FREAC-3 (FKHL7, FKH-1), FREAC-4 (FKHL8), FREAC-5 (FKHL9, FKH-2, HFH-6), FREAC-6 (FKHL10, HFH-5), FREAC-7 (FKHL11), FREAC-8 (FKHL12, HFH-7), FKH-3, FKH-4, FKH-5, HFH-1 and HFH-4.
• Human AFX1 which is involved in a chromosomal translocation that causes acute leukemia.
• Human FKHR which is involved in a chromosomal translocation that causes rhabdomyosarcoma.
• Xenopus XFKH1, a protein essential for normal axis formation.
• Caenorhabditis elegans lin-31; involved in the regulation of vulval cell fates.
• Yeast HCM1, a protein of unknown function.
• Yeast FKH1.
• Yeast FKH2.

The fork domain is highly conserved. We have developed two patterns for its detection. The first corresponds to the N-terminal section of the domain; the second is a heptapeptide located in the central section of the domain.