Dimer formation via the homeodomain is required for function and specificity of Sex combs reduced in Drosophila

► Sex combs reduced, but not its closest relative, Antennapedia, dimerizes in vivo. ► Sex combs reduced dimerization requires the conserved residue 19 of the homeodomain. ► Sex combs reduced dimerization is facilitated by DNA binding. ► Sex combs reduced homeotic function relies on dimer formation in Drosophila. ► Linker and C terminus are independently required to confer dimerization in Sex combs reduced, in the presence of glutamate 19 of the homeodomain.