homeodomain

The homeodomain is a conserved protein domain of about 60 amino acids found in a large family of transcription factors that regulate development and cell fate. It is encoded by homeobox genes, including the Hox clusters, and is present in many eukaryotes, including animals, plants, and fungi.

Structurally, the homeodomain forms a helix-turn-helix fold consisting of three alpha helices. Helix 3 acts as the recognition helix that binds the major groove of DNA, typically recognizing TAAT-containing sequences. The domain often binds DNA cooperatively with cofactors, which can influence binding specificity and target selection. The DNA-binding activity is modular, occurring in the context of larger transcription factors that contain additional activation or repression domains.

Functionally, homeodomain-containing transcription factors regulate pattern formation and organ development. In animals, Hox proteins and related factors control segment identity and the formation of appendages and tissues; in plants, homeodomain proteins participate in meristem maintenance and morphogenesis; in fungi, they participate in developmental and mating-type processes.

The domain is highly conserved, reflecting a common mechanism of DNA interaction, yet specific target sequences and regulatory outcomes are diverse across lineages.

History and terminology: The term arose from studies of homeotic mutations in Drosophila, which revealed genes essential for body plan; the corresponding DNA sequence encodes a conserved homeobox that gives rise to the homeodomain in protein products. The homeobox and the homeodomain denote related but distinct concepts.