The AXH (ataxin-1 and HMG-box protein 1) domain is a module of ~130 amino acids, which has been identified in ATX1 and in the apparently unrelated transcription factor HBP1 [1]. It is found in many vertebrate and invertebrate proteins. It has been suggested that the AXH domain is a molecular scaffold domain engaged in multiple protein-protein interactions and in RNA binding.

The AXH domain consists of a noncanonical oligonucleotide and oligosaccharide binding (OB) fold. Although sharing a similar OB fold, the structure of the AXH domains from ATX1 (see <PDB:1OA8>) and HBP1 (see <PDB:1V06>) have genuinely distinct folds. The differences are not, as in other chameleon sequences, determined by a different tendency to adopt distinct secondary structures: the two folds share the same secondary structure elements, but these are differently arranged in space. The AXH domain has a chameleon structure in which the N and C termini can adopt distinctly different conformation. Neither of the differences are induced by binding to another molecule. While clearly correlated (sharing a sequence identity of ca. 30% and a homology of ca. 50% depending on the species), AXH has slightly different domain boundaries and distinct properties in ATX1 and HBP1. There is a cluster of charged residues that could constitute a ligand-binding site [2,3].

Some proteins known to contain a AXH domain are listed below:

• Animal ataxin-1 (ATX1), a neurodegenerative disorder protein whose glutamine-repeat expanded form causes spinocerebellar ataxia type 1 (SCA1) in humans and exerts cytotoxicity in Drosophila and mouse.
• Animal Brother of ataxin-1 (Boat) [4].
• Vetebrate HMG box containing protein 1 (HBP1). It is thought to be involved in an architectural regulation of chromatin and in specific gene expression.

The profile we developed covers the entire AXH domain.