The Per-Arnt-Sim (PAS) domain was identified as a 270 amino acid motif that mediates associations between various PAS family transcription factors. Several PAS domain family members have been identified including AhR, Arnt 1, and single-minded proteins (SIM1 and SIM2). The aromatic (aryl) hydrocarbon receptor, AhR, is a ligand dependent transcription factor that interacts with specific DNA sequences termed xenobiotic responsive elements (XREs) to activate several genes including CYP1A1, glutathione S-transferase Ya subunit and DT-diaphorase. The Ah receptor nuclear translocator protein 1 (Arnt 1) is required for ligand-dependent nuclear translocation of the Ah receptor and is also necessary for Ah receptor binding to the XRE element. Both SIM1 and SIM2 inhibit AhR/Arnt dimerization, thus inhibiting transcriptional activation. The SIM genes are thought to be involved in the directing and regionalization of tissues during development and the SIM2 gene, which is located on chromosome 21, is a candidate for the gene responsible for Down syndrome.