<p>Homeodomain proteins are transcription factors that share a related DNA-binding homeodomain [<cite idref="PUB00013192"/>]. The homeodomain was initially identified in <taxon tax_id="7227">Drosophila melanogaster</taxon> (Fruit fly) homeotic and segmentation proteins, but is well conserved throughout metazoans [<cite idref="PUB00000591"/>, <cite idref="PUB00005390"/>]. The homeodomain binds DNA through a helix-turn-helix (HTH) structure, consisting of approximately 20 residues [<cite idref="PUB00004373"/>]. The HTH motif is comprised of two alpha-helices that make intimate contacts with the DNA; the second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions. These interactions occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA. The first helix helps to stabilise the structure and is joined to the second through a short turn.</p><p> Most proteins which contain a homeobox domain can be classified [<cite idref="PUB00000591"/>, <cite idref="PUB00005101"/>],on the basis of their sequence characteristics, into three subfamilies, engrailed, antennapedia andpaired. A number of different proteins contain homeodomains, including Drosophila engrailed, yeast mating type proteins, hepatocyte nuclear factor 1a and Hox proteins. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies [<cite idref="PUB00010002"/>]. The homeodomain motif is very similar in sequence identity and structure to domains in other DNA-binding proteins, including recombinases, GARP response regulators, human telomeric protein, AraC type transcriptional activator and tetracycline repressor [<cite idref="PUB00013193"/>, <cite idref="PUB00013194"/>, <cite idref="PUB00003347"/>].</p><p>This entry identifies a conserved region of some 20 amino-acid residues, specific to engrailed proteins, located at the C-terminal of the 'homeobox' domain; the specific function of these residues is unclear.</p> Homeobox engrailed-type, conserved site