The fork head domain is a conserved DNA-binding domain (also known as a "winged helix") of about 100 amino-acid residues.
Drosophila melanogaster fork head protein is a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors [ (PUBMED:2566386) ]. Instead, it contains a distinct type of DNA-binding region, containing around 100 amino acids, which has since been identified in a number of transcription factors (including D. melanogaster FD1-5, mammalian HNF-3, human HTLF, Saccharomyces cerevisiae HCM1, etc.). This is referred to as the fork head domain but is also known as a 'winged helix' [ (PUBMED:2566386) (PUBMED:8332212) (PUBMED:1356269) ].
The fork head domain binds B-DNA as a monomer [ (PUBMED:8332212) ], but shows no similarity to previously identified DNA-binding motifs. Although the domain is found in several different transcription factors, a common function is their involvement in early developmental decisions of cell fates during embryogenesis [ (PUBMED:1356269) ].
GO process:
regulation of transcription, DNA-templated (GO:0006355)
GO function:
sequence-specific DNA binding (GO:0043565), DNA-binding transcription factor activity (GO:0003700)
Family alignment:
There are 22315 FH domains in 22242 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing FH domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with FH domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing FH domain in the selected taxonomic class.
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.
Since its discovery five years ago the conserved family of fork head/HNF-3-related transcription factors has gained increasing importance for the analysis of gene regulatory mechanisms during embryonic development and in differentiated cells. Different members of this family, which is defined by a conserved 110 amino acid residues encompassing DNA binding domain of winged helix structure, serve as regulatory keys in embryogenesis, in tumorigenesis or in the maintenance of differentiated cell states. The purpose of this review is to summarize the accumulating amount of data on structure, expression and function of fork head/HNF-3-related transcription factors.
Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5.
Nature. 1993; 364: 412-20
Display abstract
The three-dimensional structure of an HNF-3/fork head DNA-recognition motif complexed with DNA has been determined by X-ray crystallography at 2.5 A resolution. This alpha/beta protein binds B-DNA as a monomer, through interactions with the DNA backbone and through both direct and water-mediated major and minor groove base contacts, inducing a 13 degrees bend. The transcription factor fold is very similar to the structure of histone H5. In its amino-terminal half, three alpha-helices adopt a compact structure that presents the third helix to the major groove. The remainder of the protein includes a twisted, antiparallel beta-structure and random coil that interacts with the minor groove.
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 FH domain which could be assigned to a KEGG orthologous group, and not all proteins containing FH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
