A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development.

Homeoboxes are found within genes that are involved in the regulation of patterns of anatomical development (morphogenesis) in animals, fungi, plants, and numerous single cell eukaryotes.

The homeobox domain was first identified in a number of Drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates.

[9] Analysis of antennapedia revealed that this gene contained a 180 base pair sequence that encoded a DNA binding domain, which William McGinnis termed the "homeobox".

[10] The existence of additional Drosophila genes containing the antennapedia homeobox sequence was independently reported by Ernst Hafen, Michael Levine, William McGinnis, and Walter Jakob Gehring of the University of Basel in Switzerland and Matthew P. Scott and Amy Weiner of Indiana University in Bloomington in 1984.

The characteristic homeodomain protein fold consists of a 60-amino acid long domain composed of three alpha helices.

The recognition helix and the inter-helix loops are rich in arginine and lysine residues, which form hydrogen bonds to the DNA backbone.

Homeodomain proteins show a preference for the DNA sequence 5'-TAAT-3'; sequence-independent binding occurs with significantly lower affinity.

Homeodomain proteins function as transcription factors due to the DNA binding properties of the conserved HTH motif.

[17] Many homeodomain proteins induce cellular differentiation by initiating the cascades of coregulated genes required to produce individual tissues and organs.

Hox genes and their associated microRNAs are highly conserved developmental master regulators with tight tissue-specific, spatiotemporal control.

[22] It is accepted that the three major animal ANTP-class clusters, Hox, ParaHox, and NK (MetaHox), are the result of segmental duplications.

[30][31] Specific members of the Hox family have been implicated in vascular remodeling, angiogenesis, and disease by orchestrating changes in matrix degradation, integrins, and components of the ECM.

[42] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFalpha-inducible monocyte binding to HUVECs.

They function in cytoskeletal remodeling, at focal adhesion sites, as scaffolds for protein complexes, and as transcription factors.

The individual domains of POU proteins bind DNA only weakly, but have strong sequence-specific affinity when linked.

The POU domain itself has significant structural similarity with repressors expressed in bacteriophages, particularly lambda phage.

According to their conserved intron–exon structure and to unique codomain architectures they have been grouped into 14 distinct classes: HD-ZIP I to IV, BEL, KNOX, PLINC, WOX, PHD, DDT, NDX, LD, SAWADEE and PINTOX.