Doublesex (DSX) is a transcription factor that regulates somatic sexual differences in Drosophila. The structure of this domain has revealed a novel dimeric arrangement of ubiquitin-associated folds that has not previously been identified in a transcription factor [(PUBMED:16049008)].
Doublesex (DSX) is a transcription factor that regulates somatic sexual differences in Drosophila. The structure has revealed a novel dimeric arrangement of ubiquitin-associated folds that has not previously been identified in a transcription factor [ (PUBMED:16049008) ].
Family alignment:
There are 279 DSX_dimer domains in 261 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing DSX_dimer domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with DSX_dimer domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing DSX_dimer domain in the selected taxonomic class.
Dimerization of doublesex is mediated by a cryptic ubiquitin-associated domainfold: implications for sex-specific gene regulation.
J Biol Chem. 2005; 280: 32989-96
Display abstract
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.