Various levels of functional diversity in a very conserved protein family. The first line shows the canonical structure of a nuclear receptor, comprising a DNA-binding domain (DBD) and a ligand-binding domain, that are structurally well conserved. A canonical receptor represses transcription in absence of a ligand (or it is even not in the nucleus) and activates transcription upon ligand binding. The second line shows a receptor that has lost its DNA-binding domain and that acts also as a transcriptional repressor. The third line shows a receptor that is complete at the gene level, but for which the expression of one isoform starts only at the half of the DNA-binding domain. It acts also as a transcriptional repressor. The fourth line shows a receptor having lost its ligand-binding domain. The last line shows an example of receptor that still has this canonical structure, but that has no known ligand and acts also as a constitutive transcriptional repressor. Whereas knirps and tailless bind to corepressors that are not nuclear receptors, DAX-1 and E75B act as dominant negatives, blocking the activation activity of another nuclear receptor with a canonical structure.