In Drosophila, single-minded (sim) is a transcription factor that acts as the master regulator of neurogenesis. Two mammalian homologues of Sim which have been identified, Sim1 and Sim2, are novel heterodimerisation partners for ARNT in vitro, and may function both as positive and negative transcriptional regulators in vivo, during embryogenesis and in the adult organism []. SIM2 is thought to contribute to some specific Down syndrome phenotypes []. There is a high level of homology among mammalian and Drosophila sim proteins in their amino-terminal half where the conserved bHLH, PAS () and PAC motifs are present (). The PAC region occurs C-terminal to the PAS domains and are proposed to contribute to the PAS domain fold [, , ]. In contrast, the carboxy-terminal parts are only conserved in vertebrates []. The Sim1 C terminus contains a Ser-rich region, whereas the Sim2 C terminus both contain Ser/Thr-rich regions, Pro/Ser-rich regions, Pro/Ala-rich regions, and positively charged regions. Sim2s, a splice variant of Sim2, still contains the Ser/Thr- and Pro/Ser-rich regions shown to harbor repressive activities, but is missing the Pro/Ala-rich repressor region [, , ].
