Forkhead box proteins (FOX proteins) are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic development.
The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. This forkhead motif is also known as the winged helix due to the butterfly-like appearance of the loops in the protein structure of the domain. Forkhead genes are a subgroup of the helix-turn-helix class of proteins.
Many other genes encoding FOX proteins have been identified. For example,
the FOXF2 gene encodes forkhead box F2, one of many human homologues of the Drosophila melanogastertranscription factorforkhead. FOXF2 is expressed in lung and placenta.
Some FOX genes are downstream targets of the hedgehog signaling pathway, which plays a role in the development of basal cell carcinomas.
The first protein in the FOX family that was discovered was the fork head transcription factor in Drosophila (thus the name). Since then a large number of family members have been discovered, especially in vertebrates. Originally they were given vastly different names (such as HFH, FREAC, and fkh), but in 2000 a unified nomenclature was introduced that grouped the FOX proteins into subclasses (FOXA-FOXS) based on sequence conservation.