Homeobox domain, metazoa (IPR020479)

Short name: Homeobox_metazoa

Overlapping homologous superfamilies

Domain relationships


The homeobox domain (homeodomain) is a 60-residue motif first identified in a number of Drosophila homeotic and segmentation proteins, but now known to be well- conserved in many other animals, including vertebrates [PMID: 1357790, PMID: 2568852]. Proteins containing homeobox domains are likely to play an important role in development - most are known to be sequence-specific DNA-binding transcription factors. The domain binds DNA through a helix-turn-helix (HTH) structure.

The HTH motif is characterised by 2 alpha-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which 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. The motif is very similar in sequence and structure in a wide range of DNA-binding proteins (for example, cro and repressor proteins, homeotic proteins, amongst others). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn (position 9 of the motif), which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.

This entry represents the eukaryotic homeobox domain.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0003677 DNA binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.