PROSITE documentation PDOC00564 [for PROSITE entry PS50039]
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.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

FORK_HEAD_3, PS50039; Fork head domain profile  (MATRIX)

FORK_HEAD_1, PS00657; Fork head domain signature 1  (PATTERN)

FORK_HEAD_2, PS00658; Fork head domain signature 2  (PATTERN)


1AuthorsWeigel D. Jaeckle H.
TitleThe fork head domain: a novel DNA binding motif of eukaryotic transcription factors?
SourceCell 63:455-456(1990).
PubMed ID2225060

2AuthorsClark K.L. Halay E.D. Lai E. Burley S.K.
TitleCo-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5.
SourceNature 364:412-420(1993).
PubMed ID8332212

3AuthorsHaecker U. Kaufmann E. Hartmann C. Juergens G. Knoechel W. Jaeckle H.
SourceEMBO J. 14:5306-5317(1995).

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