This family represents the C-terminal region of the eukaryotic single-minded (SIM) protein. Drosophila single-minded acts as a positive master gene regulator in central nervous system midline formation. There are two homologs in mammals: SIM1 and SIM2, which are members of the basic-helix-loop-helix PAS family of transcription factors. SIM1 and SIM2 are novel heterodimerization partners for ARNT in vitro, and they 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. This family is found in conjunction with a pfam00989 domain and associated pfam00785 motif.