Forkhead Domains


The forkhead domain or box represents an evolutionarily conserved DNA‐binding motif of winged helix structure that has a degree of similarity to the helix–turn–helix motif found in other DNA‐binding proteins. Forkhead box (Fox) proteins are involved in a variety of biological processes such as early embryogenesis, organogenesis, tumorigenesis and signal transduction.

Keywords: transcription factors; gene regulation; DNA–protein interaction; embryogenesis; signal transduction; tumorigenesis

Figure 1.

Structure and scheme of the forkhead/winged helix domain of HNF‐3γ (FoxA3). Structural data are from Clark et al., . Note that the forkhead domain comprises three α‐helices (H1, H2 and H3), three β‐strands (S1, S2 and S3), two wings (W1 and W2) and a turn‐like structure (T′). Main deoxyribonucleic acid (DNA) contacts are formed by H3, located within the major groove. C: carboxy‐terminus; N: amino‐terminus.



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Further Reading

Anderson MJ, Viars CS, Czekay S, Cavenee WK and Arden KC (1998) Cloning and characterization of three human forkhead genes that comprise an FKHR‐like gene subfamily. Genomics 47: 187–199.

Brennan RG (1993) The winged‐helix DNA‐binding motif: another helix–turn–helix takeoff. Cell 74: 773–776.

Brunet A, Bonni A, Zigmond MJ, et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96: 857–868.

Gajiwala KS, Chen H, Cornille F, et al. (2000) Structure of the winged‐helix protein hRFX1 reveals a new mode of DNA binding. Nature 403: 916–921.

Hatini V, Huh SO, Herzlinger D, Soares VC and Lai E (1996) Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF‐2. Genes and Development 10: 1467–1478.

Kaestner KH, Katz J, Liu Y, Drucker DJ and Schütz G (1999) Inactivation of the winged helix transcription factor HNF3α affects glucose homeostasis and islet glucagon gene expression in vivo. Genes and Development 13: 495–504.

Kume T, Deng K and Hogan BL (2000) Minimal phenotype of mice homozygous for a null mutation in the forkhead/winged helix gene, Mf2. Molecular and Cellular Biology 20: 1419–1425.

Murakami S, Tedesco PM, Cypser JR and Johnson TE (2000) Molecular genetic mechanisms of life span manipulation in Caenorhabditis elegans. Annals of the New York Academy of Sciences 908: 40–49.

Overdier DG, Porcella A and Costa RH (1994) The DNA‐binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino‐acid residues adjacent to the recognition helix. Molecular and Cellular Biology 14: 2755–2766.

Xuan S, Baptista CA, Balas G, et al. (1995) Winged helix transcription factor BF‐1 is essential for the development of the cerebral hemispheres. Neuron 14: 1141–1152.

Web Links

forkhead box A2 (FOXA2); LocusID: 3170. LocusLink:

forkhead box C1 (FOXC1); LocusID: 2296. LocusLink:

forkhead box E1 (FOXE1); LocusID: 2304. LocusLink:

forkhead box O1A (FOXO1a); LocusID: 2308. LocusLink:

paired box gene 3 (PAX3); LocusID: 5077. LocusLink:

forkhead box A2 (FOXA2); MIM number: 600288. OMIM:‐post/Omim/dispmim?600288

forkhead box C1 (FOXC1); MIM number: 601090. OMIM:‐post/Omim/dispmim?601090

forkhead box E1 (FOXE1); MIM number: 602617. OMIM:‐post/Omim/dispmim?602617

forkhead box O1A (FOXO1a); MIM number: 136533. OMIM:‐post/Omim/dispmim?136533

paired box gene 3 (PAX3); MIM number: 193500. OMIM:‐post/Omim/dispmim?193500

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How to Cite close
Kaufmann, Eckhard, and Knöchel, Walter(Sep 2005) Forkhead Domains. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005052]