{{short description|DNA-binding protein domain found in transcription factors}} {{Pfam_box | Symbol = Fork_head | Name = Fork head domain | image = PDB_2hfh_EBI.jpg | width = | caption = Structure of the winged helix protein Genesis.<ref name="pmid9571051">{{cite journal |vauthors=Marsden I, Jin C, Liao X |title=Structural changes in the region directly adjacent to the DNA-binding helix highlight a possible mechanism to explain the observed changes in the sequence-specific binding of winged helix proteins |journal=J. Mol. Biol. |volume=278 |issue=2 |pages=293–9 |date=May 1998 |pmid=9571051 |doi=10.1006/jmbi.1998.1703 }}</ref> | Pfam = PF00250 | InterPro = IPR001766 | SMART = SM00339 | PROSITE = PDOC00564 | SCOP = 2hfh | TCDB = | OPM family = | OPM protein = | CDD = cd00059 | PDB = {{PDB2|1d5v}}, {{PDB2|1e17}}, {{PDB2|1jxs}}, {{PDB2|1kq8}}, {{PDB2|2a3s}}, {{PDB2|2c6y}}, {{PDB2|2d2w}}, {{PDB2|2hdc}}, {{PDB2|2hfh}} }}
The '''fork head domain''' is a type of protein domain that is often found in transcription factors and whose purpose is to bind DNA.<ref name="pmid8817449">{{cite journal | vauthors = Kaufmann E, Knöchel W | title = Five years on the wings of fork head | journal = Mech. Dev. | volume = 57 | issue = 1 | pages = 3–20 |date=June 1996 | pmid = 8817449 | doi = 10.1016/0925-4773(96)00539-4 | s2cid = 18056224 | doi-access = free }}</ref>
== Function ==
The fork head protein of ''Drosophila melanogaster'', a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors.<ref name="pmid2566386">{{cite journal | vauthors = Weigel D, Jürgens G, Küttner F, Seifert E, Jäckle H | title = The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo | journal = Cell | volume = 57 | issue = 4 | pages = 645–58 |date=May 1989 | pmid = 2566386 | doi = 10.1016/0092-8674(89)90133-5| doi-access = free }}</ref> 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 HNF3, human HTLF, ''Saccharomyces cerevisiae'' HCM1, etc.). This is referred to as the fork head domain but is also known as a "winged helix".<ref name="pmid2566386"/><ref name="pmid8332212">{{cite journal | vauthors = Clark KL, Halay ED, Lai E, Burley SK | title = Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5 | journal = Nature | volume = 364 | issue = 6436 | pages = 412–20 |date=July 1993 | pmid = 8332212 | doi = 10.1038/364412a0 | s2cid = 4363526 }}</ref><ref name="pmid1356269">{{cite journal | vauthors = Häcker U, Grossniklaus U, Gehring WJ, Jäckle H | title = Developmentally regulated Drosophila gene family encoding the fork head domain | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 89 | issue = 18 | pages = 8754–8 |date=September 1992 | pmid = 1356269 | pmc = 49999 | doi = 10.1073/pnas.89.18.8754| doi-access = free }}</ref> The fork head domain binds B-DNA as a monomer,<ref name="pmid8332212"/> 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.<ref name="pmid1356269"/> Members of the class O of forkhead box transcription factors (FoxO) have important roles in metabolism, cellular proliferation, stress tolerance and probably lifespan.<ref name="pmid17522590">{{cite journal | vauthors = van der Horst A, Burgering BM | title = Stressing the role of FoxO proteins in lifespan and disease | journal = Nature Reviews Molecular Cell Biology | volume = 8 | issue = 6 | pages = 440–50 |date=June 2007 | pmid = 17522590 | doi = 10.1038/nrm2190 | s2cid = 31546098 }}</ref>
== See also == * FOX proteins
== References == {{Reflist|2}}
{{InterPro content|IPR001766}}
Category:Protein domains