Taxonomic distribution of proteins containing DSX_dimer domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing DSX_dimer domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Dimerization of doublesex is mediated by a cryptic ubiquitin-associated domainfold: implications for sex-specific gene regulation.

Bayrer JR, Zhang W, Weiss MA
J Biol Chem. 2005; 280: 32989-96

Male- and female-specific isoforms of the Doublesex (DSX) transcription factorregulate somatic sexual differentiation in Drosophila. The isoforms (DSX(M) andDSX(F)) share an N-terminal DNA binding domain (the DM motif), broadly conserved among metazoan sex-determining pathways. DM-DNA recognition is enhanced by aC-terminal dimerization domain. The crystal structure of this domain, determined at a resolution of 1.6 A, reveals a novel dimeric arrangement ofubiquitin-associated (UBA) folds. Although this alpha-helical motif is wellcharacterized in pathways of DNA repair and subcellular trafficking, to ourknowledge this is its first report in a transcription factor. Dimerization ismediated by a non-canonical hydrophobic interface extrinsic to the putativeubiquitin binding surface. Key side chains at this interface, identified byalanine scanning mutagenesis, are conserved among DSX homologs. The mechanism of dimerization is thus unrelated to the low affinity domain swapping observed amongubiquitin-associated CUE domains. The unexpected observation of aubiquitin-associated fold in DSX extends the repertoire of alpha-helicaldimerization elements in transcription factors. The possibility that theubiquitination machinery participates in the regulation of sexual dimorphism isdiscussed.