Forkhead Box Proteins

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Ribbon model of the FOXO4 protein-DNA complex according to PDB 3BPY

The forkhead box proteins (FOX) are proteins in eukaryotes that attach themselves to certain parts of the DNA in the cell nucleus and thereby influence the transcription of genes (so-called transcription factors ). They regulate such important functions as proliferation , differentiation and cell life. Many FOX proteins play an important role in embryonic development.

The group of FOX proteins is characterized by a monomeric DNA binding domain consisting of around 100 amino acids. The DNA binding domain consists of a variant of the helix-turn-helix motif , which consists of three helices and two characteristic large loops , which is therefore also known as the winged helix DNA-binding domain .

The DNA binding domain of the FOX proteins has hardly changed in the course of evolution , which is why the nucleotide sequences of the genes coding for it have remained the same and the corresponding gene segment is referred to as a forkhead box .


The first protein from the forkhead family to be described was the Drosophila transcription factor forkhead, discovered by Detlef Weigel and Herbert Jäckle . The name derives from the fork-shaped ( engl. Fork = "fork") change of the head (engl. Head = "head"), which arises when Drosophila embryos the forkhead missing gene.

Since then, a large number of FOX proteins have been discovered specifically in vertebrates. Originally, very different names were used for this, such as HFH, FREAC and fkh. In 2000, a uniform nomenclature was agreed in which these proteins were divided into subclasses from FOXA to FOXR.

Previously known forkhead box proteins


  • P. Carlsson, M. Mahlapuu: Forkhead transcription factors: key players in development and metabolism. In: Dev. Biol. , 2002, 250 (1): 1-23. PMID 12297093
  • OJ Lehmann et al .: Fox's in development and disease. In: Trends Genet. , 2003, 19 (6): 339-344. PMID 12801727

Individual evidence

  1. a b K. H. Kaestner et al .: Unified nomenclature for the winged helix / forkhead transcription factors. In: Genes Dev. (2000) 14 (2): 142-146. PMID 10702024
  2. D. Weigel, H. Jäckle: The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? In: Cell . (1990) 63 (3): 455-456. PMID 2225060
  3. D. Weigel et al .: The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. In: Cell. (1989) 57 (4): 645-658. PMID 2566386