Fork head domain

The fork head domain is a type of protein domain that is often found in transcription factors and whose purpose is to bind DNA.[2]

Fork head domain
Structure of the winged helix protein Genesis.[1]
Identifiers
SymbolFork_head
PfamPF00250
InterProIPR001766
SMARTSM00339
PROSITEPDOC00564
SCOP22hfh / SCOPe / SUPFAM
CDDcd00059
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1d5v​, 1e17​, 1jxs​, 1kq8​, 2a3s​, 2c6y​, 2d2w​, 2hdc​, 2hfh​

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.[3] 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".[3][4][5] The fork head domain binds B-DNA as a monomer,[4] 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.[5] Members of the class O of forkhead box transcription factors (FoxO) have important roles in metabolism, cellular proliferation, stress tolerance and probably lifespan.[6]

See also

References
  1. Marsden I, Jin C, Liao X (May 1998). "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". J. Mol. Biol. 278 (2): 293–9. doi:10.1006/jmbi.1998.1703. PMID 9571051.
  2. Kaufmann E, Knöchel W (June 1996). "Five years on the wings of fork head". Mech. Dev. 57 (1): 3–20. doi:10.1016/0925-4773(96)00539-4. PMID 8817449. S2CID 18056224.
  3. Weigel D, Jürgens G, Küttner F, Seifert E, Jäckle H (May 1989). "The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo". Cell. 57 (4): 645–58. doi:10.1016/0092-8674(89)90133-5. PMID 2566386.
  4. Clark KL, Halay ED, Lai E, Burley SK (July 1993). "Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5". Nature. 364 (6436): 412–20. doi:10.1038/364412a0. PMID 8332212. S2CID 4363526.
  5. Häcker U, Grossniklaus U, Gehring WJ, Jäckle H (September 1992). "Developmentally regulated Drosophila gene family encoding the fork head domain". Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8754–8. doi:10.1073/pnas.89.18.8754. PMC 49999. PMID 1356269.
  6. van der Horst A, Burgering BM (June 2007). "Stressing the role of FoxO proteins in lifespan and disease". Nature Reviews Molecular Cell Biology. 8 (6): 440–50. doi:10.1038/nrm2190. PMID 17522590. S2CID 31546098.
This article incorporates text from the public domain Pfam and InterPro: IPR001766
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